Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 1 of 67
(https://www.aetna.com/)
Epilepsy Surgery
Number: 0394
Policy *Please see amendment for Pennsylvania Medicaid at the end of this CPB.
I. Ep ilepsy Surgery
Aetna considers cerebral hemispherectomy, corpus
callosotomy, and temporal lobectomy (including
selective amygdalohippocampectomy) medically
necessary when all of the following selection criteria are
met:
A. Non-epileptic attacks such as cardiogenic syncope
and psychogenic seizures have been ruled out; and
B. The diagnosis of epilepsy has been documented, and
the epileptic seizure type and syndrome has been
clearly defined. In general, appropriate candidates
for epilepsy surgery are members who are
incapacitated by their frequent seizures as well as
the toxicity of anti-epileptic drugs. The general
characteristics of individuals for each type of surgical
procedure for epilepsy are as follows:
1. Cerebral hemispherectomy: Members with
unilateral multi-focal epilepsy associated with
Policy History
Last Review
04/10/2019
Effective: 03/06/2000
Next
Review: 04/10/2020
Review History
Definitions
Additional Information
Clinical Policy Bulletin
Notes
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 2 of 67
infantile hemiplegia (especially in
hemimegalencephaly and Sturge-Weber disease);
2. Corpus callosotomy: Members with focal to
bilateral seizures (formerly known as secondarily
generalized seizures);
3. Temporal lobectomy: Members with focal
impaired awareness seizures (formerly known as
complex partial seizures) of temporal or extra-
temporal origin; and
C. Members' quality of life may significantly improve
with surgery; and
D. Seizures occur at a frequency that interferes with
members' daily living and threatens their well being;
and
E. There must have been an adequate period
of therapy of two or more antiepileptic drugs,
namely, the correct drugs used in the correct dosage,
carefully monitored for treatment effects and
members' compliance.
Aetna considers cerebral hemispherectomy, corpus callosotomy,
and temporal lobectomy (including selective
amygdalohippocampectomy) experimental and investigational
when selection criteria are not met.
II. Deep Brain Stimulation
Aetna considers deep brain stimulation medically
necessary for members with intractable seizures. (See
CPB 0208 - Deep Brain Stimulation
(../200_299/0208.html)
III. Localized Neocortical Resections
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 3 of 67
Aetna considers localized neocortical resections experimental
and investigational for uncontrolled focal impaired awareness
seizures (formerly complex partial seizures) because its
effectiveness has not been established.
IV. Hippocampal Electrical Stimulation
Aetna considers hippocampal electrical stimulation for the
treatment of mesial temporal lobe epilepsy experimental and
investigational because its effectiveness has not been established.
V. Responsive Cortical Stimulation
Aetna considers responsive cortical stimulation/responsive
neurostimulation (e.g., the NeuroPace RNS System) medically
necessary for adults with intractable focal aware seizures
(formerly partial seizures (motor or sensory)) or focal impaired
awareness seizures (formerly complex partial seizures) (with
motor manifestations)) with or without focal to bilateral seizures
(formerly known as secondarily generalized seizures) when the
following criteria are met:
A. Non-epileptic attacks such as cardiogenic syncope
and psychogenic seizures have been ruled out; and
B. The diagnosis of epilepsy has been documented, and
the epileptic seizure type and syndrome has been
clearly defined. In general, appropriate candidates
for responsive cortical stimulation are members who
are incapacitated by their frequent seizures as well
as the toxicity of anti-epileptic drugs; and
C. The member has been diagnosed with no more than
two epileptogenic regions; and
D. Member has one of the following indications for
responsive cortical stimulation:
1. Independent onset of left and right temporal lobe
onset seizures in persons who are not candidates
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 4 of 67
for resection due to the loss of memory and
language that bilateral temporal resection is
known to cause; or
2. Left temporal lobe onset seizures where there is
concern of language or memory impairment with
a resection based upon WADA testing and the
rest of the diagnostic work up; or
3. More than one zone of ictal onset, either
temporal lobe, neocortical, or both, clearly
localized by intracranial recordings, MEG, or other
suitable presurgical evaluation making surgical
resection unlikely to be successful; or
4. A well-defined neocortical focus for seizures, with
or without anatomic abnormality on
neuroimaging, either with or without overlap of
eloquent cortex; and.
E. Member has seizures that are severe enough to
cause injuries or significantly impair functional ability
in domains including employment, psychosocial,
education and mobility; and
F. Members' quality of life may significantly improve
with responsive cortical stimulation; and
G. There must have been an adequate period
of therapy of two or more antiepileptic drugs,
namely, the correct drugs used in the correct dosage,
carefully monitored for treatment effects and
members' compliance; and
H. Member does not have an electronic medical device
that delivers electrical energy to the head; and
I. Member's s eizure onset zones a re not located below
the level of the subthalamic nucleus (lead placement
would present too high a risk).
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 5 of 67
Aetna considers responsive cortical stimulation experimental and
investigational for primary generalized seizures and for all other
indications.
VI. Stereotactic Radiosurgery
Aetna considers the use of stereotactic radiosurgery
including radiofrequency amygdalohippocampectomy
for medial temporal lobe epilepsy and epilepsy arising
in other functional cortical regions experimental and
investigational because its effectiveness for these
indications has not been established
(see CPB 0083 - Stereotactic Radiosurgery (../1_99/0083.html))
VII. Stem Cell Therapy and Gene Therapy
Aetna considers stem cell therapy as well as gene therapy for the
treatment of refractory epilepsy experimental and investigational
because their effectiveness has not been established.
VIII.Trigeminal Nerve Stimulation
Aetna considers trigeminal nerve stimulation experimental and
investigational for members with intractable seizures because its
effectiveness has not been established.
IX. S ubpial Transection Surgery
Aetna considers subpial transection surgery for refractory
epilepsy experimental and investigational because its
effectiveness has not been established.
X. High-frequency Oscillations
Aetna considers the use of high-frequency oscillations in
epilepsy surgery planning experimental and investigational
because its effectiveness has not been established.
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 6 of 67
XI. Magnetic Resonance-guided Laser Interstitial Thermal
Th erapy
Aetna considers magnetic resonance-guided laser interstitial
thermal therapy (MRgLITT) (e.g. the NeuroBlate and the
Visualase Thermal Therapy System) medically necessary as an
alternative to standard surgery where criteria in section I on
epilepsy surgery are met.
Note: The Wada test (intra-carotid amobarbital procedure),
part of the pre-surgical evaluation of members who may
undergo temporal lobectomy, is considered a medically
necessary service.
Note: Examination of genetic variations in members with
refractory epilepsy to guide the selection of surgical
candidates is considered experimental and investigational
because the effectiveness of this approach has not been
established.
See also:
•
CPB 0191 - Vagus Nerve Stimulation
(../100_199/0191.html)
•
CPB 0208 - Deep Brain Stimulation
(../200_299/0208.html)
•
CPB 0221 - Quantitative EEG (Brain Mapping)
(../200_299/0221.html)
•
CPB 0322 - Electroencephalographic (EEG) Video
Monitoring (0322.html)
•
CPB 0425 - Ambulatory Electroencephalography
(../400_499/0425.html)
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 7 of 67
•
CPB 0469 - Transcranial Magnetic Stimulation and
Cranial Electrical Stimulation (../400_499/0469.html)
, and
•
CPB 0781 - Interstitial Laser Therapy
(../700_799/0781.html)
Background
For patients who have intractable seizures despite adequate
treatment with appropriate antiepileptic drugs, surgery is their
last hope. The goal of epilepsy surgery is not only to decrease
the frequency of seizures, but also to improve quality of life.
Temporal lobectomy has been found to be safe and effective
for treating patients with complex partial seizures of temporal
or extratemporal origin. Patients who have a single identifiable
focus in a restricted cortical area that can be safely excised
without producing additional disability can be considered as
candidates for temporal lobectomy.
Corpus callosotomy has been found to be safe and effective
for treating patients with partial and secondarily general ized
seizures.
There is only limited evidence that cerebral hemispherectomy
is effective in managing unilateral multi-focal epilepsy
associated with infantile hemiplegia (especially in
hemimegalencephaly and Sturge-Weber disease). However, it
is the last hope for these patients to eliminate/alleviate their
disabling epileptic seizures, and to avoid adverse irreversible
psychosocial consequences that may lead to lifelong disability.
Since the advent of deep brain stimulation (DBS) for the
treatment of a variety of movement disorders, studies have
been performed to ascertain whether this method can reduce
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 8 of 67
seizure frequency. Evidence from experimental animal studies
suggests the existence of a nigral control of the epilepsy
system. The results of animal studies are promising, but work
on humans is preliminary.
In a pilot study, Boon et al (2007) assessed the effectiveness
of long-term DBS in medial temporal lobe (MTL) structures in
patients with MTL epilepsy. A total of 12 consecutive patients
with refractory MTL epilepsy were included in this study. The
protocol included invasive video-EEG monitoring for ictal-onset
localization and evaluation for subsequent stimulation of the
ictal-onset zone. Side effects and changes in seizure
frequency were carefully monitored. Ten of 12 patients
underwent long-term MTL DBS; 2 of 12 patients underwent
selective amygdalo-hippocampectomy. After mean follow-up
of 31 months (range of 12 to 52 months), 1 of 10 stimulated
patients was seizure-free (more than 1 year), 1 of 10 patients
had a greater than 90 % reduction in seizure frequency; 5 of
10 patients had a seizure-frequency reduction of greater than
equal to 50 %; 2 of 10 patients had a seizure-frequency
reduction of 30 to 49 %; and 1 of 10 patients was a non-
responder. None of the patients reported side effects. In 1
patient, magnetic resonance imaging (MRI) showed
asymptomatic intra-cranial hemorrhages along the trajectory of
the DBS electrodes. None of the patients showed changes in
clinical neurological testing. Patients who underwent selective
amygdalo-hippocampectomy are seizure-free (more than 1
year), anti-epileptic drugs are unchanged, and no side effects
have occurred. The authors concluded that this open pilot
study demonstrated the potential efficacy of long-term DBS in
MTL structures that should now be further confirmed by multi-
center randomized controlled trials (RCTs).
The Wada test (intra-carotid amytal procedure) is commonly
used as a predictor of memory dysfunction following temporal
lobectomy for intractable epilepsy. Asymmetry in memory
scores can provide focus lateralizing information.
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 9 of 67
The Agency for Healthcare Research and Quality's technology
assessment on the management of treatment-resistant
epilepsy stated that the data are inconsistent across studies
and do not allow for firm evidence-based conclusions as to the
exact proportion of patients who will become seizure-free or
who will not benefit from multiple subpial transection. In
addition, too few studies were available to allow for an evidence-
based evaluation of parietal or occipital lobe surgery (Chapell et
al, 2003). The American Academy of Neurology (AAN)'s
practice parameter on temporal lobe and localized neocortical
resections for epilepsy stated that there remains no Class I or II
evidence regarding the safety and efficacy of localized
neocortical resections. Further studies are needed to determine
if neocortical seizures benefit from surgery (Engel et al, 2003).
Candidates for epilepsy surgery and their family, if applicable,
should receive detailed information regarding the specific
surgical procedures and their possible benefits and side
effects. Candidates for epilepsy surgery should not have co-
existent progressive neurological disease or major
psychological or medical disorder. Persons with progressive
neurological diseases or major medical or psychological
disorders are generally unsuitable candidates for epilepsy
surgery because of the possibility that surgery could worsen
the course of these other conditions.
In a pilot study (n = 5), Velasco and colleagues (2005)
examined the safety and effectiveness of cerebellar
stimulation (CS) on patients with medically refractory motor
seizures, and especially generalized tonic-clonic seizures.
Bilateral modified 4-contact plate electrodes were placed on
the cerebellar superomedial surface through 2 sub-occipital
burr holes. The implanted programmable, battery-operated
stimulator was adjusted to 2.0 microC/cm2/phase with the
stimulator case as the anode; at this level, no patient
experienced the stimulation. Patients served as their own
controls, comparing their seizure frequency in pre-implant
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 10 of 67
basal phase (BL) of 3 months with the post-implant phases
from 10 months to 4 years (average, 8 epochs of 3 months
each). During the month after implantation, the stimulators
were not activated. The patient and the evaluator were
blinded as to the next 3-month epoch, as to whether
stimulation was used. The patients were randomized into 2
groups: (i) 3 with the stimulator ON, and (ii) 2 with the
stimulator OFF. After a 4-month post-implantation period, all
patients had their stimulator ON until the end of the study and
beyond. Medication was maintained unchanged throughout
the study. EEG paroxysmal discharges also were measured.
Generalized tonic-clonic seizures: in the initial 3-month double-
blind phase, 2 patients were monitored with the stimulation
OFF; no change was found in the mean seizure rate (patient 1,
100 %, and patient 5, 85 %; mean, 93 %), whereas the 3
patients with the stimulation initially ON had a reduction of
seizures to 33 % (patient 2, 21 %; patient 3, 46 %; patient 4,
32 %) with a statistically significant difference between OFF
and ON phase of p = 0.023. All 5 patients then were
stimulated and monitored. At the end of the next 6 months of
stimulation, the 5 patients had a mean seizure rate of 41 %
(14 to 75 %) of the BL. The second patient developed an
infection in the implanted s ystem, which had to be removed
after 11 months of stimulation; the seizures were being
reduced with stimulation to a mean of 1 per month from a
mean of 4.7 per month (BL level) before stimulation. At the
end of 24 months, 3 patients were monitored with stimulation,
resulting in a further reduction of seizures to 24 % (1 1 to 38
%). Tonic seizures: 4 patients had these seizures, which at 24
months were reduced to 43 % (10 to 76 %). Follow-up surgery
was necessary in 4 patients because of infection in 1 patient
and lead/electrode displacement needing repositioning in 3
patients. The statistical analysis showed a significant
reduction in tonic-clonic seizures (p < 0.001) and tonic
seizures (p < 0.05). These investigators concluded that the
superomedial cerebellar cortex appears to be a safe and
effective target for electrical stimulation for decreasing motor
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 11 of 67
seizures over the long-term. The effect shows generalized
tonic-clonic seizure reduction after 1 to 2 months and
continues to decrease over the first 6 months and then
maintains this effectiveness over the study period of 2 years
and beyond. The results of this pilot study needed to be
validated by additional trials with larger patient populations.
Fountas et al (2010) reviewed the pertinent literature to outline
the role of CS in the management of medically refractory
epilepsy. The pertinent articles were categorized into 2 large
groups: (i) animal experimental and (ii) human clinical
studies. Particular emphasis on the following aspects was
given when reviewing the human clinical studies: their
methodological characteristics, the number of participants,
their seizure types, the implantation technique and its
associated complications, the exact stimulation target, the
stimulation technique, the seizure outcome, and the patients'
psychological and social post-stimulation status. Three clinical
double-blind studies were found, with similar implantation
surgical technique, stimulation target, and stimulation
parameters, but quite contradictory results. Two of these
studies failed to demonstrate any significant seizure reduction,
whereas the third one showed a significant post-stimulation
decrease in seizure frequency. All possible factors
responsible for these differences in the findings were analyzed
in the present study. The authors concluded that CS seems to
remain a stimulation t arget worth exploring for defining its
potential in the treatment of medically intractable epilepsy,
although the data from the double-blind clinical studies that
were performed failed to establish a clear benefit in regard to
seizure frequency. They noted that a large-scale, double-blind
clinical study is needed for accurately defining the efficacy of
CS in epilepsy treatment.
Electrical stimulation of the hippocampus has been proposed
as a possible treatment for mesial temporal lobe epilepsy
(MTLE). Tellez-Zenteno et al (2006) reported their findings of
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 12 of 67
4 patients with refractory MTLE (whose risk to memory
contraindicated temporal lobe resection) who underwent
implantation of a chronic stimulating depth electrode along the
axis of the left hippocampus. These investigators used
continuous, sub-threshold electrical stimulation (90 microsec,
190 Hz) and a double-blind, multiple cross-over, randomized
controlled design, consisting of 3 treatment pairs, each
containing two 1-month treatment periods. During each
treatment pair, the stimulator was randomly turned ON 1
month and OFF 1 month. Outcomes were assessed at
monthly intervals in a double-blind manner, using standardized
instruments and accounting for a washout period. These
researchers compared outcomes between ON, OFF, and
baseline periods. Hippocampal stimulation produced a
median reduction in seizures of 15 %. All but 1 patient's
seizures improved; however, the results did not reach
significance.Effects seemed to carry over into the OFF
period, and an implantation effect can not be ruled out. These
researchers found no significant differences in other
outcomes. There were no adverse effects. One patient has
been treated for 4 years and continued to experience
substantial long-term seizure improvement. The authors
demonstrated important beneficial trends, some long-term
benefits, and absence of adverse effects of hippocampal
electrical stimulation in MTLE. However, the effect sizes
observed were smaller than those reported in non-
randomized, unblinded studies. They stated that large scale,
double-blind RCTs are needed to ascertain the effectiveness
of hippocampal electrical stimulation in patients with MTLE.
Velasco and colleagues (2007) evaluated the safety and
effectiveness of electrical stimulation of the hippocampus in a
long-term follow-up study, as well as its impact on memory
performance in the treatment of patients with refractory MTLE.
A total of 9 patients were included. All had refractory partial
complex seizures, some with secondary generalizations. All
patients had a 3-month-baseline-seizure count, after which
they underwent bilateral hippocampal diagnostic electrode
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 13 of 67
implantation to establish focus laterality and location -- 3
patients had bilateral; 6 had unilateral foci. Diagnostic
electrodes were explanted and definitive Medtronic electrodes
were implanted directed into the hippocampal foci. Position
was confirmed with MRI and afterwards, the DBS system
internalized. Patients attended a medical appointment every 3
months for seizure diary collection, DBS system checkup, and
neuropsychological testing. Follow-up ranged from 18 months
to 7 years. Patients were divided in 2 groups: (i) 5 had
normal MRIs and seizure reduction of greater than 95 %,
and (ii) 4 had hippocampal sclerosis and seizure reduction
of 50 to 70 %. No patient had neuropsychological
deterioration, nor did any patient show side effects. Three
patients were explanted after 2 years due to skin erosion in the
trajectory of the system. The authors concluded that electrical
stimulation of the hippocampus provides a non-lesional
method that improves seizure outcome without memory
deterioration in patients with hippocampal epileptic foci. This
is a small study; its findings need to be validated by studies
with larger patient populations.
Sun and associates (2008) stated that with the success of
DBS for treatment of movement disorders, brain stimulation
has received renewed attention as a potential treatment option
for epilepsy. Responsive stimulation aims to suppress
epileptiform activity by delivering stimulation directly in
response to electrographic activity. Animal and human data
support the concept that responsive stimulation can abort
epileptiform activity, and this modality may be a safe and
effective treatment option for epilepsy. Responsive stimulation
has the advantage of specificity. In contrast to the typically
systemic administration of pharmacotherapy, with the
concomitant possibility of side effects, electrical stimulation
can be targeted to the specific brain regions involved in the
seizure. In addition, responsive stimulation provides temporal
specificity. Treatment is provided as needed, potentially
reducing the likelihood of functional disruption or habituation
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 14 of 67
due to continuous treatment. The authors reviewed current
animal and human research in responsive brain stimulation for
epilepsy and discussed the NeuroPace RNS System, an
investigational implantable responsive neurostimulator system
that is being evaluated in a multi-center, randomized, double-
blinded trial to assess the safety and efficacy of responsive
stimulation for the treatment of medically refractory epilepsy.
Morrell et al (2011) evaluated the safety and effectiveness of
responsive cortical stimulation as an adjunctive therapy for
partial onset seizures in adults with medically refractory
epilepsy. A total of 191 adults with medically intractable partial
epilepsy were implanted with a responsive neurostimulator
connected to depth or subdural leads placed at 1 or 2 pre-
determined seizure foci. The neurostimulator was
programmed to detect abnormal electrocorticographic activity.
One month after implantation, subjects were randomized 1:1
to receive stimulation in response to detections (treatment) or
to receive no stimulation (sham). Safety and effectiveness
were assessed over a 12-week blinded period and a
subsequent 84-week open-label period during which all
subjects received responsive stimulation. Seizures were
significantly reduced in the treatment (-37.9 %, n = 97)
compared to the sham group (-17.3 %, n = 94; p = 0.012)
during the blinded period and there was no difference between
the treatment and sham groups in adverse events. During the
open-label period, the seizure reduction was sustained in the
treatment group and seizures were significantly reduced in the
sham group when stimulation began. There were significant
improvements in overall quality of life (p < 0.02) and no
deterioration in mood or neuropsychological function. The
authors concluded that responsive cortical stimulation reduces
the frequency of disabling partial seizures, is associated with
improvements in quality of life, and is well-tolerated with no
mood or cognitive effects. They noted that responsive
stimulation may provide another adjunctive treatment option
for adults with medically intractable partial seizures. However,
with its more invasive surgical component, this approach
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 15 of 67
(responsive cortical stimulation) carries greater risks and
requires careful patient selection; identification of factors
prdicting good outcome prior to electrode implantation would
be of great value. Furthermore, responsive cortical stimulation
has yet to be approved for use in the U.S.
Gamma knife (GK) radiosurgery has been proposed as an
alternative to classic microsurgery in MTLE. Bartolomei and
colleagues (2008) reported the efficacy and tolerance of GK
radiosurgery in MTLE after a follow-up of more than 5 years.
A total of 15 patients were included in this study; 8 were
treated on the left side, and 7 were treated on the right. The
mean follow-up was 8 years (range of 6 to 10 years). At the
last follow-up, 9 of 16 patients (60 %) were considered seizure-
free (Engel Class I) (4/16 in Class IA, 5/16 in Class IB).
Seizure cessation occurred with a mean delay of 12 months
(+/- 3) after GK radiosurgery, often preceded by a period of
increasing aura or seizure occurrence (6/15 patients). The
mean delay of appearance of the first neuroradiological
changes was 12 months (+/- 4). Nine patients (60 %)
experienced mild headache and were placed on corticosteroid
treatment for a short period. All patients who were initially
seizure-free experienced a relapse of isolated aura (10/15, 66
%) or complex partial seizures (10/15, 66 %) during anti-
epileptic drug tapering. Restoration of treatment resulted in
good control of seizures.
In an editorial that accompanied the afore-mentioned paper,
Spencer (2008) stated that "gamma knife treatment in mesial
temporal lobe epilepsy, then, is still searching for a place.
Right now, its disadvantages (slightly lower seizure response
rate, delayed response, absolute requirement for continued
medications, higher mortality) compared to anterior medial
temporal resection seem to outweigh its noninvasive status,
which so far does not appear to carry any clear benefits in
terms of neurologic or cognitive function, or seizure response.
Whether gamma knife treatment should be considered for
intractable epilepsy arising in other functional cortical regions
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 16 of 67
that can notbe treated with resection remains unexplored. Its
efficacy, as well as morbidity, in those situations has not been
examined, and the volume and definition of the tissues to be
targeted are considerably less well-defined than for mesial
lobe epilepsy".
In a pilot study, Barbaro et al (2009) reported the 3-year
outcomes of a multi-center, study of GK radiosurgery for
MTLE. Radiosurgery was randomized to 20 or 24 Gy targeting
the amygdala, hippocampus, and parahippocampal gyrus.
Seizure diaries evaluated the final seizure remission between
months 24 and 36. Verbal memory was evaluated at baseline
and 24 months with the Wechsler Memory Scale-Revised
(WMS-R) and California Verbal Learning Test (CVLT).
Patients were classified as having "significant improvement,"
"no change," and "significant impairment" based on relative
change indices. Thirteen high-dose and 17 low-dose patients
were treated. Both groups showed significant reductions in
seizures by 1 year after treatment. At the 36-month follow-up
evaluation, 67 % of patients were seizure-free for the prior 12
months (high-dose: 10/13, 76.9 %; low-dose: 10/17, 58.8 %).
Use of steroids, headaches, and visual field defects did not
differ by dose or seizure remission. The prevalence of verbal
memory impairment was 15 % (4/26 patients); none declined
on more than 1 measure. The prevalence of significant verbal
memory improvements was 12 % (3/26). The authors
concluded that GK radiosurgery for unilateral MTLE offers
seizure remission rates comparable with those reported
previously for open surgery. There were no major safety
concerns with high-dose radiosurgery compared with low-dose
radiosurgery. They stated that additional research is needed
to determine if GK radiosurgery may be a treatment option for
some patients with MTLE.
Vojtech et al (2009) examined the effectiveness of GK
radiosurgery in the treatment of MTLE due to mesial temporal
sclerosis. A total of 14 patients underwent radiosurgical
entorhino-amygdalo-hippocampectomy with a marginal dose
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 17 of 67
of 18-, 20-, or 25-Gy to the 50 % isodose following a standard
pre-operative epilepsy evaluation. One patient was classified
as Engel Class Ib, 3 were Engel Class IIc, 1 was Engel Class
IIIa, and 2 were Engel Class IVb in a subgroup of 7 patients
who were unoperated 2 years prior to the last visit and at least
8 years after irradiation (average of 116 months). The
insufficient effect of irradiation led these investigators to
perform epilepsy surgery on another 7 patients an average of
63.5 months after radiosurgery. The average follow-up period
was 43.5 months after the operation. Four patients are seizure
free; 1 is Engel Class IIb and 1 is Engel Class IId. One patient
can not be classified due to the short period of follow-up. The
frequency of seizures tended to rise after irradiation in some
patients. Collateral edema was observed in 9 patients, which
started earlier and was more frequent in those irradiated with
higher doses. It had a marked expansive character in 3 cases
and clinical signs of intra-cranial hypertension were present in 3
cases. Partial upper lateral
quadrant anopia as a permanent side effect was observed in 2
patients. Repeated psychotic episodes (2 patients) and status
epilepticus (2 patients) were also seen after treatment. No
significant memory changes occurred in the group as a whole.
The authors concluded that radiosurgery with 25-, 20, or 18
Gy marginal dose levels did not lead to seizure control in this
patient series, although subsequent epilepsy surgery could
stop seizures. Higher doses were associated with the risk of
brain edema, intra-cranial hypertension, and a temporary
increase in seizure frequency.
Malikova et al (2009) described MRI changes following
stereotactic radiofrequency amygdalohippocampectomy (AHE)
and correlated the hippocampal and amygdalar volumes
reduction with the clinical seizure outcome. A total of 18
patients were included. Volumetry was calculated from pre-
operative MRI and from MRI obtained 1 year after the
operation. The clinical outcome was examined 1 and 2 years
after the treatment. Hippocampal volume decreased by 54 +/-
19 %, and amygdalar volume decreased by 49 +/- 18 %. One
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 18 of 67
year after the procedure, 13 (72 %) patients were classified as
Engel's Class I (9 as Class IA), 4 (22 %) patients as Class II
and 1 (6 %) patient as Class III. Two years after the operation,
14 patients (82 %) were classified as Class I (7 as Class IA)
and 3 patients (18 %) as Class II. There were 3 surgical
complications after the procedure: 1 small subdural
hematoma, and twice a small electrode tip left in operation
field (these patients were excluded from the study). In 3
patients, temporary meningeal syndrome developed. The
authors concluded that results of stereotactic radiofrequency
AHE are promising.
Naegele et al (2010) stated that the potential applications of
stem cell therapies for treating neurological disorders are
enormous. Many laboratories are focusing on stem cell
treatments for diseases of the central nervous system,
including amyotrophic lateral sclerosis, epilepsy, Huntington's
disease, multiple sclerosis, Parkinson's disease, spinal cord
injury, stroke, and traumatic brain injury. Among the many
stem cell types under testing for neurological treatments, the
most common are fetal and adult brain stem cells, embryonic
stem cells, induced pluripotent stem cells, and mesenchymal
stem cells. An expanding toolbox of molecular probes is now
available to allow analyses of neural stem cell fates prior to
and after transplantation. Concomitantly, protocols are being
developed to direct the fates of stem cell-derived neural
progenitors, and also to screen stem cells for tumorigenicity
and aneuploidy. The rapid progress in the field suggested that
novel stem cell therapy as well as gene therapy for
neurological disorders are in the pipeline.
Tellez-Zenteno and Wiebe (2011) stated that hippocampal
stimulation should be regarded as an experimental therapy for
epilepsy, and patients considered for this intervention should
do so in the contextof a well-designed RCT. The authors
concluded that only well-conducted, blinded, randomized trials,
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 19 of 67
followed by long-term systematic observation will yield a clear
picture of the effect of this promising therapy, and will help
guide its future use.
In a pilot feasibility study, Degiorgio et al (2006) evaluated the
safety and preliminary effectiveness of trigeminal nerve
stimulation (TNS) of the infra-orbital and supra-orbital
branches of the trigeminal nerve for the treatment of epilepsy.
Trigeminal nerve stimulation was well-tolerated. Four (57 %)
of 7 subjects who completed greater than or equal to 3 months
experienced a greater than or equal to 50 % reduction in
seizure frequency. The authors concluded that the results of
this pilot study supported further investigation into the safety
and effectiveness of TNS for epilepsy.
In a double-blind, randomized controlled trial, Degiorgio et al
(2013) examined the safety and effectiveness of external TNS
(eTNS) in patients with drug-resistant epilepsy (DRE), and
tested the suitability of treatment and control parameters in
preparation for a phase III multi-center clinical trial. A total of
50 subjects with 2 or more partial onset seizures per month
(complex partial or tonic-clonic) entered a 6-week baseline
period, and then were evaluated at 6, 12, and 18 weeks during
the acute treatment period. Subjects were randomized to
treatment (eTNS 120 Hz) or control (eTNS 2 Hz) parameters.
At entry, subjects were highly drug-resistant, averaging 8.7
seizures per month (treatment group) and 4.8 seizures per
month (active controls). On average, subjects failed 3.35 anti-
epileptic drugs prior to enrollment, with an average duration of
epilepsy of 21.5 years (treatment group) and 23.7 years
(active control group), respectively. External TNS was well-
tolerated. Side effects included anxiety (4 %), headache (4
%), and skin irritation (14 %). The responder rate, defined as
greater than 50 % reduction in seizure frequency, was 30.2 %
for the treatment group versus 21.1 % for the active control
group for the 18-week treatment period (not significant, p =
0.31, generalized estimating equation [GEE] model). The
treatment group experienced a significant within-group
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 20 of 67
improvement in responder rate over the 18-week treatment
period (from 17.8 % at 6 weeks to 40.5 % at 18 weeks, p =
0.01, GEE). Subjects in the treatment group were more likely
to respond than patients randomized to control (odds ratio
1.73, confidence interval [CI]: 0.59 to 0.51). External TNS was
associated with reductions in seizure frequency as measured
by the response ratio (p = 0.04, analysis of variance
[ANOVA]), and improvements in mood on the Beck
Depression Inventory (p = 0.02,ANOVA). The authors
concluded that the findings of this study provided preliminary
evidence that eTNS is safe and may be effective in subjects
with DRE. Side effects were primarily limited to anxiety,
headache, and skin irritation. They stated that these results
will serve as a basis to inform and power a larger multi-center
phase III clinical trial.
In an editorial that accompanied the afore-mentioned study by
Degiorgio et al, Faught and Tatum (2013) stated that “The
beneficial effect demonstrated by Degiorgio et al was modest,
but is sufficient to encourage design of a more definitive
study”.
Liu and associates (2013) stated that with an annual incidence
of 50/100,000 people, nearly 1 % of the population suffers
from epilepsy. Treatment with anti-epileptic medication fails to
achieve seizure remission in 20 to 30 % of patients. One
treatment option for refractory epilepsy patients who would not
otherwise be surgical candidates is electrical stimulation of the
brain, which is a rapidly evolving and reversible adjunctive
therapy. Therapeutic stimulation can involve direct stimulation
of the brain nuclei or indirect stimulation of peripheral nerves.
There are 3 stimulation modalities that have class I evidence
supporting their uses: (i) vagus nerve stimulation (VNS), (ii)
stimulation of the anterior nuclei of the thalamus (ANT),
and, (iii) the most recently developed, responsive
neurostimulation (RNS). While the other treatment
modalities outlined deliver stimulation regardless of neuronal
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 21 of 67
activity, the RNS administers stimulation only if triggered by
seizure activity. The lower doses of stimulation provided by
such responsive devices can not only reduce power
consumption, but also prevent adverse reactions caused by
continuous stimulation, which include the possibility of
habituation to long-term stimulation. Responsive
neurostimulation, as an investigational treatment for medically
refractory epilepsy, is currently under review by the Food and
Drug Administration.
Ge and colleagues (2013) reviewed the targets of the deep
brain and RNS to identify the best optimal stimulation
parameters and the best mode of stimulation, whether cyclical,
continuous, or smarter. This review was based on data
obtained from published articles from 1950 to 2013. To
perform the PubMed literature search, the following keywords
were input: deep brain stimulation (DBS), RNS, and refractory
epilepsy. Articles containing information related to brain
stimulation or RNS for the treatment of refractory epilepsy
were selected. The currently available treatment options for
those patients who resist multiple anti-epileptic medications
and surgical procedures include electric stimulation, both
direct and indirect, of brain nuclei thought to be involved in
epileptogenesis. The number of potential targets has
increased over the years to include the ANT, the centromedian
nucleus of the thalamus, the hippocampus, the subthalamic
nucleus, the caudate nucleus, and the cerebellum, among
others. The results of a RCT and the RNS trial were published
to reveal the effectiveness. The authors concluded that
although statistically significant reductions in seizures had
been observed using several different stimulation techniques,
including VNS, DBS, and RNS, these effects are currently only
palliative and do not approach the effectiveness comparable
with that seen in resection in appropriately selected patients.
They stated that more research is needed to determine
optimal stimulation targets and techniques as well as to
determine which epilepsy patients will benefit most from this
technology.
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 22 of 67
Krishnaiah and co-workers (2013) stated that nearly 30 % of
patients with epilepsy continue to have seizures in spite of
several anti-epileptic drug (AED) regimens. In such cases
they are regarded as having refractory, or uncontrolled
epilepsy. There is no universally accepted definition for
uncontrolled or medically refractory epilepsy, but for the
purpose of this review, these investigators considered seizures
to be drug resistant if they failed to respond to a minimum of 2
AEDs. It is believed that early surgical intervention may
prevent seizures at a younger age and improve the intellectual
and social status of children. There are many types of surgery
for refractory epilepsy with subpial transection being one. In a
Cochrane review, these researchers determined the benefits
and adverse effects of subpial transection for partial-onset
seizures and generalized tonic-clonic seizures in children and
adults. They searched the Cochrane Epilepsy Group
Specialised Register (August 8, 2013), the Cochrane Central
Register of Controlled Trials (CENTRAL Issue 7 of 12, The
Cochrane Library July 2013), and MEDLINE (1946 to August
8, 2013). They did not impose any language restrictions.
These investigators considered all randomized and quasi-
randomized parallel group studies either blinded or non-
blinded. Two review authors independently screened the trials
identified by the search. The same 2 authors planned to
independently assess the methodological quality of studies. If
studies had been identified for inclusion, 1 author would have
extracted the data and the other would have verified it. No
relevant studies were found. The authors concluded that there
is no evidence to support or refute the use of subpial
transection surgery for medically refractory cases of epilepsy.
Moreover, they stated that well-designed RCTs are needed to
guide clinical practice.
Gloss and colleagues (2014) stated that approximately 2/3 of
seizures can be controlled with anti-epileptic medications. For
some of the others, surgery can completely eliminate or
significantly reduce the occurrence of disabling seizures.
Localization of epileptogenic areas for resective surgery is far
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 23 of 67
from perfect, and new tools are being investigated to more
accurately localize the epileptogenic zone and improve the
likelihood of freedom from post-surgical seizures. Recordings
of pathological high-frequency oscillations (HFOs) may be one
such tool. In a Cochrane review, these investigators evaluated
the ability of HFOs to improve the outcomes of epilepsy
surgery by helping to identify more accurately the
epileptogenic areas of the brain. They searched the Cochrane
Epilepsy Group Specialized R egister (April 15, 2013), the
Cochrane Central Register of Controlled T rials (CENTRAL) in
The Cochrane Library (2013, Issue 3 ), MEDLINE (Ovid) (1946
to April 15, 2013), CINAHL (EBSCOhost) (April 15, 2013),
Web of Knowledge (Thomson R euters) (April 15, 2013),
www.clinicaltrials.gov (April 15, 2013), and the World Health
Organization International Clinical Trials Registry Platform
(April 15, 2013). These researchers included s tudies that
provided information on the outcomes of epilepsy surgery at 6
months or more and which used HFOs in making decisions
about epilepsy surgery. The primary outcome of the review
was the Engel Class Outcome System. Secondary outcomes
were responder rate, International League Against Epilepsy
(ILAE) epilepsy surgery outcome, frequency of adverse events
from any source and quality of life outcomes. They intended
to analyze outcomes via an aggregated data fixed-effect
model meta-analysis. Two studies met the inclusion criteria.
Both studies were small non-randomized trials, with no control
group and no blinding. The quality of evidence for all
outcomes was very low. The combination of these 2 studies
resulted in 11 participants who prospectively used ictal HFOs
for epilepsy surgery decision making. Results of the post-
surgical seizure freedom Engel class I to IV outcome were
determined over a period of 12 to 38 months (average of 23.4
months) and indicated that 6 participants had an Engel class I
outcome (seizure freedom), 2 had class II (rare disabling
seizures), 3 had class III (worthwhile improvement). No
adverse effects were reported. Neither study compared
surgical re sults guided by HFOs versus surgical re sults guided
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 24 of 67
without HFOs. The authors concluded that no reliable
conclusions can be drawn regarding the effectiveness of using
HFOs in epilepsy surgery decision making at present.
The NeuroPace RNS System is a responsive cortical
stimulator for the treatment of medically intractable partial
epilepsy. The RNS System includes a cranially implanted
programmable neurostimulator that is connected to one or two
depth and/or subdural cortical strip leads that are surgically
placed in or on the brain at the seizure focus. The
neurostimulator continuously senses brain electrical activity
through the leads. When abnormal brain electrical activity
typical of the activity that precedes that patient's seizures is
detected, the neurostimulator delivers pulses of stimulation
through those same electrodes before an individual
experiences seizures.
Heck et al (2014) sought to evaluate the safety and
effectiveness of responsive s timulation at the seizure focus as
an adjunctive therapy to reduce the frequency of seizures in
adults with medically intractable partial onset seizures arising
from 1 or 2 seizure foci. The investigators conducted a
randomized multi-center double-blinded controlled t rial of
responsive focal cortical stimulation (RNS System). Subjects
with medically intractable partial onset seizures from 1 or 2 foci
were implanted, and 1 month post-implant were randomized
1:1 to active or sham stimulation. After the 5th post-implant
month, all subjects received responsive s timulation i n an open
label period (OLP) to complete 2 years of post-implant follow-
up. All 191 subjects were randomized. The percent change in
seizures at the end of the blinded period w as -37.9 % in the
active and -17.3 % in the sham stimulation group (p = 0.012,
Generalized Estimating Equations). The median percent
reduction in seizures in the OLP was 44 % at 1 year and 53 %
at 2 years, which represents a progressive and significant
improvement with time (p < 0.0001). The investigators
reported that serious adverse event rate was not different
between subjects receiving active and sham stimulation.
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 25 of 67
Adverse events were consistent with the known risks of an
implanted medical device, seizures, and of other epilepsy
treatments. There were no adverse effects on
neuropsychological function or mood.
Bergey et al (2014) assessed the long-term efficacy and safety
of responsive direct cortical stimulation in adults with medically
refractory partial onset seizures. Adults with medically
refractory partial onset seizures were treated with a cranially
implanted r esponsive neu rostimulator that delivers stimulation
to 1 or 2 seizure foci via chronically implanted electrodes when
specific electrocorticographic patterns are detected (RNS®
System). Subjects had completed a 2-year primarily open
label safety study (n = 65) or a 2-year randomized blinded
controlled safety and efficacy study (n = 191); 230 subjects
transitioned into an ongoing 7-year long-term study to assess
safety and efficacy. The average subject was 34 years old (18
to 66) with epilepsy for 19.6 years (2 to 57). The median pre-
implant frequency of disabling partial or generalized tonic
clonic seizures was 10.2 seizures a month. Prior treatments
included the vagus nerve stimulator (32 %) and epilepsy
surgery (34 %). Mean post-implant follow-up was 4.7 years (5
weeks to 8.6 years) with an accumulated experience of 1,199
patient implant years and 1,107 patient stimulation years. The
median percent seizure r eduction in the randomized bl inded
controlled trial at 1 year was 44 % and at 2 years was 53 % (p
< 0.0001 GEE) and ranged from 55 % to 60 % over post-
implant years 3 through 6 for patients followed in the long-term
study. Significant improvements in quality of life (QOL) were
maintained (p < 0.05). The most common serious adverse
events related to the device in all studies combined were
implant site infection (8.2 %) and neurostimulator explantation
(3.9 %).
Patients with RNS Stimulators cannot undergo magnetic
resonance imaging (MRI) procedures, nor can they undergo
diathermy procedures, electro-convulsive therapy (ECT) or
transcranial magnetic stimulation (TMS). The energy created
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 26 of 67
from these procedures can be sent through the
neurostimulator and cause permanent brain damage, even if
the device is turned off. The most frequent adverse events
reported in clinical trials of the Neuropace were implant site
infection and premature battery depletion.
The AAN’s practice parameter on “Temporal lobe and
localized neocortical resections for epilepsy” (Engel et al,
2003) supported surgery (including
amygdalohippocampectomy) for refractory TLE.
Maguire et al (2011) stated that “There is consensus that
amygdalohippocampectomy is likely to be beneficial for people
with drug-resistant temporal lobe epilepsy”.
Kuang et al (2014) noted that TLE is a recurrent chronic
nervous system disease. The conventional treatment is
medicine. So far,anterior temporal lobectomy (ATL) and
selective amygdalohippocampectomy (SAH; removal of the
amygdala and hippocampus only) are becoming the 2 main
approaches. These investigators compared the therapeutic
effects between SAH and ATL in the treatment of TLE. They
conducted a meta-analysis of published RCTs. The review
applied the search strategy developed by the Cochrane
Epilepsy Group and the Rev. Man 5.0 software to analyze.
These researchers also drew the forest plots with Risk Ratio
(RR) as effect size. A total of 6 studies were eligible, with a
total of 626 patients (337 patients with SAH and 289 patients
with ATL). There was no statistical significance of post-
operative seizure control rate after 1 year, as well as the
increase rate and decrease rate of verbal memory function
between SAH and ATL. There is no statistical difference of
therapeutic effects between SAH and ATL in the treatment of
TLE. The authors concluded that it is advised that clinically,
physicians should choose the appropriate approach according
to operation indications to improve the results of post
operative recovery.
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 27 of 67
Kovanda et al (2014) stated that a number of different surgical
techniques are effective for treatment of drug-resistant MTLE.
Of these, trans-sylvian SAH, which was originally developed to
maximize temporal lobe preservation, is arguably the most
technically demanding to perform. Recent studies have
suggested that SAH may result in better neuropsychological
outcomes with similar post-operative seizure control as
standard ATL, which involves removal of the lateral temporal
neocortex. These investigators described technical nuances
to improve the safety of SAH. Wide sylvian fissure opening
and use of neuro-navigation allows an adequate exposure of
the amygdala and hippocampus through a corticotomy within
the inferior insular sulcus. Avoidance of rigid retractors and
careful manipulation and mobilization of middle cerebral
vessels will minimize ischemic complications. Identification of
important landmarks during amygdalohippocampectomy, such
as the medial edge of the tentorium and the third nerve within
the intact arachnoid membranes covering the brainstem,
further avoids operator disorientation. The authors concluded
that SAH is a safe technique for resection of medial temporal
lobe epileptogenic foci leading to drug-resistant MTLE.
Malikova et al (2014) compared 2 different surgical
approaches, standard microsurgical ATL and stereotactic
radiofrequency SAHE for MTLE, with respect to the extent of
resection or destruction, clinical outcomes, and complications.
A total of 75 MTLE patients were included: 41 treated by SAH
(11 right-sided, 30 left-sided) and 34 treated by ATL (21 right-
sided, 13 left-sided). SAH and ATL seizure control were
comparable (Engel I in 75.6 and 76.5 % 2 years after surgery
and 79.3 and 76.5 % 5 years after procedures, respectively).
The neuropsychological results of SAH patients were better
than in ATL. In SAH patients, no memory deficit was found.
Hippocampal (60.6 ± 18.7 %) and amygdalar (50.3 ± 21.9 %)
volume reduction by SAH was significantly lower than by ATL
(86.0 ± 12.7 % and 80.2 ± 20.9 %, respectively). The overall
rate of surgical non-silent complications without permanent
neurological deficit after ATL was 11.8 %, and another 8.8 %
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 28 of 67
silent infarctions were found on MRI. The rate of clinically
manifest complications after SAH was 4.9 %. The rate of
visual field defects after SAH was expectably less frequent
than after ATL. The authors concluded that seizure control by
SAH was comparable to ATL. However, SAH was safer with
better neuropsychological results.
Jobst and Cascino (2015) reviewed resective surgery
outcomes for focal epilepsy to identify which patients benefit
the most. These investigators noted that similar procedures
such as selective amygdalohippocampectomy and temporal
lobectomy for TLE were associated with subtle differences in
seizure and neuropsychological outcome.
Laser Amygdalohippocampectomy
Willie and colleagues (2014) described technical and clinical
outcomes of stereotactic laser amygdalohippocampotomy with
real-time MR thermal imaging guidance. With patients under
general anesthesia and using standard stereotactic methods,
a total of 13 adult patients with intractable MTLE (with and
without mesial temporal sclerosis [MTS]) prospectively
underwent insertion of a saline-cooled fiber-optic laser
applicator in amygdalohippocampal structures from an
occipital trajectory. Computer-controlled laser ablation was
performed during continuous MR thermal imaging followed by
confirmatory contrast-enhanced anatomic imaging and
volumetric reconstruction. Clinical outcomes were determined
from seizure diaries. A mean 60 % volume of the
amygdalohippocampal complex was ablated in 13 patients (9
with MTS) undergoing 15 procedures. Median hospitalization
was 1 day. With follow-up ranging from 5 to 26 months
(median of 14 months), 77 % (10/13) of patients achieved
meaningful seizure reduction, of whom 54 % (7/13) were free
of disabling seizures. Of patients with pre-operative MTS, 67
% (6/9) achieved seizure freedom. All recurrences were
observed before 6 months. Variances in ablation volume and
length did not account for individual clinical outcomes.
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 29 of 67
Although no complications of laser therapy itself were
observed, 1 significant complication, a visual field defect,
resulted from deviated insertion of a stereotactic aligning rod,
which was corrected before ablation. The authors concluded
that real-time MR-guided stereotactic laser
amygdalohippocampotomy is a technically novel, safe, and
effective alternative to open surgery. They stated that further
evaluation with larger cohorts over time is needed.
Mathon and associates (2015) reviewed the published
literature related to the outcome of the surgical treatment of
MTLE associated with hippocampal sclerosis (HS) and
described the future prospects in this field. Surgery of MTLE
associated with HS achieves long-term seizure freedom in
about 70 % (62 to 83 %) of cases. Seizure outcome is similar
in the pediatric population. Mortality following temporal
resection is very rare (less than 1 %) and the rate of definitive
neurological complication is low (1 %). Gamma knife
stereotactic radiosurgery used as a treatment for MTLE would
have a slightly worse outcome to that of surgical resection, but
would provide neuropsychological advantage. However, the
average latency before reducing or stopping seizures is at
least 9 months with radiosurgery. Regarding palliative
surgery, amygdalohippocampal stimulation has been
demonstrated to improve the control of epilepsy in carefully
selected patients with intractable MTLE who are not
candidates for resective surgery. Recent progress in the field
of imaging and image-guidance should allow to elaborate
tailored surgical strategies for each patient in order to achieve
seizure freedom. Concerning therapeutics, closed-loop
stimulation strategies allow early seizure detection and
responsive stimulation. It may be less toxic and more effective
than intermittent and continuous neuro-stimulation. Moreover,
stereotactic radiofrequency amygdalohippocampectomy is a
recent approach leading to hopeful results. Closed-loop
stimulation and stereotactic radiofrequency
amygdalohippocampectomy may provide a new treatment
option for patients with drug-resistant MTLE. The authors
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 30 of 67
concluded that mesial temporal lobe surgery has been widely
evaluated and has become the standard treatment for MTLE
associated with HS. Alternative surgical procedures like
gamma knife stereotactic radiosurgery and
amygdalohippocampal stimulation are currently under
assessment, with promising results.
Chang et al (2015) noted that surgery can be a highly effective
treatment for medically refractory TLE. The emergence of
minimally invasive resective and non-resective therapeutic
options has led to interest in epilepsy surgery among patients
and providers. Nevertheless, not all procedures are
appropriate for all patients, and it is critical to consider seizure
outcomes with each of these approaches, as seizure freedom
is the greatest predictor of patient quality of life. Standard ATL
remains the gold standard in the treatment of TLE, with seizure
freedom resulting in 60 to 80 % of patients. It is currently the
only resective epilepsy surgery supported by RCTs and offers
the best protection against lateral temporal seizure onset.
Selective amygdalohippocampectomy techniques preserve
the lateral cortex and temporal stem to varying degrees and
can result in favorable rates of seizure freedom but the risk of
recurrent seizures appears slightly greater than with ATL, and
it is unclear if neuropsychological outcomes are improved with
selective approaches. Stereotactic radiosurgery presents an
opportunity to avoid surgery altogether, with seizure outcomes
now under investigation. Stereotactic laser thermo-ablation
allows destruction of the mesial temporal structures with low
complication rates and minimal recovery time, and outcomes
are also under study. Finally, while neuromodulatory devices
such as responsive neuro-stimulation, vagal nerve stimulation,
and deep brain stimulation hav e a r ole in the treatment of
certain patients, these remain palliative pr ocedures for those
who are not candidates for resection or ablation, as complete
seizure freedom rates are low. The authors concluded that
further development and investigation of both established and
novel strategies for the surgical treatment of TLE will be critical
moving forward, given the significant burden of this disease.
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 31 of 67
Magnetic Resonance-Guided Laser Interstitial Thermal Therapies
Lewis and colleagues (2015) reported the feasibility, safety,
and clinical outcomes of an exploratory study of magnetic
resonance-guided laser interstitial thermal therapy (MRgLITT)
as a minimally invasive surgical procedure for the ablation of
epileptogenic foci in children with drug-resistant, lesional
epilepsy. These investigators performed a retrospective chart
review of all MRgLITT procedures at a single tertiary care
center. All procedures were performed using a Food and Drug
Administration (FDA)-cleared surgical laser ablation system
(Visualase Thermal Therapy System). Pre-defined clinical and
surgical variables were extracted from archived medical
records. A total of 17 patients underwent 19 MRgLITT
procedures from May 2011 to January 2014. Mean age at
seizure onset was 7.1 years (range of 0.1 to 14.8). Mean age
at surgery was 15.3 years (range of 5.9 to 20.6). Surgical
substrates were mixed but mainly composed of focal cortical
dysplasia (n = 11); complications occurred in 4 patients.
Average length of hospitalization post-surgery was 1.56 days.
Mean follow-up was 16.1 months (n = 16; range of 3.5 to
35.9). Engel class I outcome was achieved in 7 patients (7/17;
41 %), Engel class II in 1 (1/17; 6 %), Engel class III in 3 (3/17;
18 %), and Engel class IV in 6 (6/17; 35 %); 3 patients (3/8; 38
%) with class I and II outcomes and 5 patients (5/9; 56 %) with
class III and IV outcomes had at least 1 prior resection.
Fisher's exact test was not statistically significant for the
association between Engel class outcome and previous
resection (p = 0.64). The authors concluded that this study
provided descriptive results regarding the use of MRgLITT in a
mixed population of pediatric, lesional, drug-resistant epilepsy
cases. The ability to classify case-specific outcomes and
reduce technical complications is anticipated as experience
develops. They stated that further multi-center, prospective
studies are needed to delineate optimal candidates for
MRgLITT, and larger cohorts are needed to more accurately
define outcome and complication rates.
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 32 of 67
Kang et al (2016) described mesial temporal lobe ablated
volumes, verbal memory, and surgical outcomes in patients
with medically intractable MTLE treated with MRI-guided
stereotactic laser interstitial thermal therapy (LiTT). These
researchers prospectively tracked seizure outcome in 20
patients with drug-resistant MTLE who underwent MRI-guided
LiTT from December 2011 to December 2014. Surgical
outcome was assessed at 6 months, 1 year, 2 years, and at
the most recent visit. Volume-based analysis of ablated
mesial temporal structures was conducted in 17 patients with
MTS and results were compared between the seizure-free and
not seizure-free groups. Following LiTT, proportions of
patients who were free of seizures impairing consciousness
(including those with auras only) are as follows: 8 of 15
patients (53 %, 95 % CI: 30.1 to 75.2 %) after 6 months, 4 of
11 patients (36.4 %, 95 % CI: 14.9 to 64.8 %) after 1 year, 3 of
5 patients (60 %, 95 % CI: 22.9 to 88.4 %) at 2-year follow-up.
Median follow-up was 13.4 months after LiTT (range of 1.3
months to 3.2 years). Seizure outcome after LiTT suggested
an all or none response; 4 patients had anterior temporal
lobectomy (ATL) after LiTT; 3are seizure-free. There were no
differences in total ablated volume of the
amygdalohippocampus complex or individual volumes of
hippocampus, amygdala, entorhinal cortex, para-hippocampal
gyrus, and fusiform gyrus between seizure-free and non-
seizure-free patients. Contextual verbal memory performance
was preserved after LiTT, although decline i n non-contextual
memory task scores were noted. The authors concluded that
MRI-guided stereotactic LiTT is a safe alternative to ATL in
patients with medically intractable MTLE. Individualized
assessment is needed to examine if the reduced odds of
seizure freedom are worth the reduction in risk, discomfort,
and recovery time. Moreover , they stated that larger
prospective studies are needed to confirm these preliminary
findings, and to define optimal ablation volume and i deal
structures for ablation.
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 33 of 67
McCracken and colleagues (2016) noted that surgery is
indicated for cerebral cavernous malformations (CCM) that
cause medically refractory epilepsy. Real-time magnetic
resonance thermography (MRT)-guided stereotactic laser
ablation (SLA) is a minimally invasive approach to treating
focal brain lesions; SLA of CCM has not previously been
described. These researchers described MRT-guided SLA, a
novel approach to treating CCM-related epilepsy, with respect
to feasibility, safety, imaging, and seizure control in 5
consecutive patients. Patients with medically refractory
epilepsy undergoing standard pre-surgical evaluation were
found to have corresponding lesions fulfilling imaging
characteristics of CCM and were prospectively enrolled. Each
underwent stereotactic placement of a saline-cooled cannula
containing an optical fiber to deliver 980-nm diode laser
energy via twist drill craniostomy; MR anatomic imaging was
used to evaluate targeting prior to ablation. Magnetic
resonance imaging provided evaluation of targeting and near
real-time feedback regarding extent of tissue
thermocoagulation. Patients maintained seizure diaries, and
remote imaging (6 to 21 months post-ablation) was obtained in
all patients. Imaging revealed no evidence of acute
hemorrhage following fiber placement within presumed CCM;
MRT during treatment and immediate post-procedure imaging
confirmed desired extent of ablation. These investigators
identified no adverse events or neurological deficits; 4 of 5 (80
%) patients achieved freedom from disabling seizures after
SLA alone (Engel class 1 outcome), with follow-up ranging 12
to 28 months. Re-imaging of all subjects (6 to 21 months)
indicated lesion diminution with surrounding liquefactive
necrosis, consistent with the surgical goal of extended
lesionotomy. The authors concluded that minimally invasive
MRT-guided SLA of epileptogenic CCM is a potentially safe
and effective alternative to open resection; additional
experience and longer follow-up are needed.
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 34 of 67
LaRiviere and Gross (2016) stated that epilepsy is a common,
disabling illness that is refractory to medical treatment in
approximately 1/3 of patients, particularly among those with
MTL epilepsy. While standard open mesial temporal
resection is effective, achieving s eizure freedom in most
patients, efforts to develop safer, minimally invasive
techniques have been underway for over 50 years.
Stereotactic ablative techniques, in particular, radiofrequency
(RF) ablation, were first developed in the 1960s, with
refinements in the 1990s with the advent of modern computed
tomography and magnetic resonance-based i maging. In the
past 5 years, the most recent techniques have used MRI-
guided laser interstitial thermotherapy (LITT), the development
of which began in the 1980s, saw refinements in MRI thermal
imaging through the 1990s, and was initially used primarily for
the treatment of intra-cranial and extra-cranial tumors. The
authors described the original stereotactic ablation trials,
followed by modern imaging-guided RF ablation series for
MTL epilepsy, and reviewed the 2 currently available MRI-
guided LITT systems for their role in the treatment of MTL and
other medically refractory epilepsies. These investigators
noted that the use of laser ablation for mesial temporal
sclerosis is only in its infancy, but its superior targeting and
intra-operative feedback control makes it an exciting candidate
for further investigation. A prospective trial comparing MRI-
guided stereotactic laser ablation with open mesial temporal
lobectomy would be i nstrumental in demonstrating the safety
and effectiveness of this promising new technique for the
treatment of epilepsy. Other clinical trial approaches will be
necessary to demonstrate relative safety and effectiveness
with respect to standard open resection techniques. However,
it must be considered that the comparison of minimally
invasive techniques is not solely to standard open techniques
but also to continued medical therapy, as there is a significant
number of patients as well as referring physicians who
consider the risk, discomfort, or inconvenience of conventional
resective surgery preclusive.
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 35 of 67
Waseem and co-workers (2017) stated that there is a new
focus on minimally invasive treatments for medically refractory
MTLE; and MRgLITT is one such minimally invasive procedure
that utilizes MRI guidance and real-time feedback to ablate an
epileptogenic focus. A total of 38 patients presenting
exclusively with MTLE and no other lesions (including
neoplasia), who underwent MRgLITT were reviewed. These
investigators evaluated a number of outcome measures,
including seizure f reedom, neuropsychological performance,
complications, and other considerations; 18 (53 %) had an
Engel class I outcome, 10 patients had repeat
procedures/operations, and 12 post-procedural complications
occurred. Follow-up time ranged from 6 to 38.5 months.
There was a decreased length of procedure time,
hospitalization t ime, and analgesic requirement when
compared to open surgery. The authors stated that in cases
of well-localized MTLE this procedure may offer similar (albeit
slightly lower) rates of seizure freedom versus traditional
surgery. They concluded that MRgLITT may be an alternative
treatment option for high-risk surgical patients and, more
importantly, could increase r eferrals for surgery in patients with
medically refractory MTLE, however, data are limited and long-
term outcomes have not been evaluated. They stated that
further investigation is needed t o understand t he potential of
this minimally invasive technique for MTLE.
Lagman and associates (2017) stated that MRgLITT is a novel
minimally invasive modality that uses heat from laser probes to
destroy tissue. Advances in probe design, cooling
mechanisms, and real-time MRT have increased laser
utilization in neurosurgery. The authors performed a
systematic analysis of 2 commercially available MRgLITT
systems used in neurosurgery: (i) the Visualase thermal
therapy and (ii) the NeuroBlate Systems. Data extraction
was performed in a blinded fashion. A total of 22 articles were
included in the quantitative synthesis. A total of 223 patients
were identified with the majority having undergone treatment
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 36 of 67
with Visualase (n = 154, 69 %). Epilepsy was the most
common indication for Visualase therapy (8 studies, 47 %).
Brain mass was the most common indication for NeuroBlate
therapy (3 studies, 60 %). There were no significant
differences, except in age, wherein the NeuroBlate group was
nearly twice as old as the Visualase group (p < 0.001). Frame,
total complications, and length-of-stay (LOS) were non-
significant when adjusted for age and number of patients. The
authors concluded that laser neurosurgery has evolved over
recent decades; clinical indications are currently being defined
and will continue to emerge as laser technologies become
more sophisticated.
Hoppe and co-workers (2017) noted that in common with other
stereotactic procedures, stereotactic laser thermocoagulation
(SLT) promises gentle destruction of pathological tissue, which
might become especially relevant for epilepsy surgery in the
future. Compared to standard resection, no large craniotomy
is necessary, cortical damage during access to deep-seated
lesions can be avoided and interventions close to eloquent
brain areas become possible. These researchers described
the history and rationale of laser neurosurgery as well as the 2
available SLT systems (Visualase and NeuroBlate). Both
systems are coupled with MRI and MR thermometry, thereby
increasing patient safety. These investigators reported the
published clinical experiences with SLT in epilepsy surgery
(altogether approximately 200 cases) with respect to
complications, brain structural alterations, seizure outcome,
neuropsychological findings and treatment costs. They stated
that the rate of seizure-free patients appeared to be slightly
lower than for resection surgery; however, due to the
inadequate quality of studies, the neuropsychological
superiority of SLT has not yet been unambiguously
demonstrated.
Shukla and colleagues (2017) noted that medically intractable
epilepsy is associated with increased morbidity and mortality.
For those with focal epilepsy and correlated
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 37 of 67
electrophysiological or radiographic features, open surgical
resection can achieve high rates of seizure control, but can be
associated with neurologic deficits and cognitive effects.
Recent innovations have allowed for more minimally invasive
methods of surgical seizure control such as MRgLITT, which
achieves the goal of ablating seizure foci while pr eserving
neuropsychological function and offering real-time feedback
and monitoring of tissue ablation. These investigators
summarized the utilization of MRgLITT for mesial temporal
lobe epilepsy and other seizure disorders. Based on studies
of laser ablation for primary glial neoplasms in adults,
MRgLITT for focal epilepsy stemming from low-grade
glioneuronal tumors in children is under study. The full range
of applications of MRgLITT in the context of medically
refractory epilepsy is still being explored. The authors
concluded that MRgLITT is a safe and effective therapeutic
option for the management of medically intractable epilepsy in
the adult and pediatric populations. Of particular significance
is the minimally invasive nature of MRgLITT, which enables
the surgical management of patients who are not good
candidates for, or are otherwise averse to, open resection.
Compared t o other minimally invasive procedures, MRgLITT
is associated with improved outcomes and better side effect
profile. While open surgical procedures have demonstrated
slightly higher rates of seizure freedom, MRgLITT is
associated with reduced hospitalization time, decreased post-
operative pain, and improved neuropsychological function.
Moreover, these researchers stated that it is important to note
that the studies reviewed were limited by small samples sizes
and the relative novelty of the procedure. Other limitations of
the currently available data include the lack of availability of
long-term outcomes data and a scarcity of RCTs. They stated
that future studies may seek to address these gaps while also
looking at questions regarding t he use of the procedure for
multi-focal epilepsy and the relationship between time from
diagnosis and MRgLITT efficacy.
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 38 of 67
Kang and Sperling (2018) noted that a procedure called laser
interstitial thermal ablation has been utilized t o treat drug
resistant epilepsy. With this technique, a probe is
stereotactically inserted into a target structure responsible for
seizures, such as mesial temporal lobe, hypothalamic
hamartoma, or a small malformation of cortical development,
and the tip is then heated by application of laser energy to
ablate structures adjacent to the probe tip. This procedure has
the advantage of selectively targeting small lesions
responsible for seizures, and is far less invasive than open
surgery with shorter hospitalization, less pain, and rapid return
to normal activities. Initial results in mesial temporal lobe
epilepsy are promising, with perhaps 50 % of patients
becoming seizure-free after the procedure.
Neuropsychological deficits appear to be reduced because of
the smaller volume of ablated cortex in contrast to large
resections. The authors concluded that more research must
be done to establish optimal targeting of structures for ablation
and selection of candidates for surgery, and more patients
must be studied to better establish efficacy and adverse effect
rates.
Cerebellar and Deep Brain Stimulation
In a Cochrane review, Sprengers and associates (2017)
evaluated the safety, efficacy, and tolerability of DBS and
cortical stimulation for refractory epilepsy based on RCTs.
These investigators searched the Cochrane Epilepsy Group
Specialized Register on September 29, 2015, but it was not
necessary to update this search, because records in the
Specialized Register are included i n CENTRAL. They
searched the Cochrane Central Register of Controlled Trials
(CENTRAL) (the Cochrane Library 2016, Issue 11, November
5, 2016), PubMed (November 5, 2016), ClinicalTrials.gov
(November 5, 2016), the World Health Organization (WHO)
International Clinical Trials Registry Platform ICTRP
(November 5, 2016) and reference lists of retrieved articles.
They also contacted device manufacturers and other
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 39 of 67
researchers in the field. No language restrictions were
imposed; RCTs comparing DBS or cortical stimulation versus
sham stimulation, resective surgery, further treatment with
anti-epileptic drugs or other neurostimulation t reatments
(including vagus nerve stimulation). Four review authors
independently selected t rials for inclusion; 2 review authors
independently extracted the relevant data and assessed trial
quality and overall quality of evidence. The outcomes
investigated were seizure freedom, responder rate,
percentage seizure frequency reduction, adverse ev ents
(AEs), neuropsychological outcome and QOL. If additional
data were needed, the study investigators were contacted.
Results were analyzed and reported separately for different
intra-cranial targets for reasons of clinical heterogeneity. A
total of 12 RCTs were identified, 11of these compared 1 to 3
months of intra-cranial neurostimulation with sham stimulation.
One trial was on anterior thalamic DBS (n = 109; 109
treatment periods); 2 trials on centromedian thalamic DBS (n =
20; 40 treatment periods), but only 1 of the trials (n = 7; 14
treatment periods) reported sufficient information for inclusion
in the quantitative meta-analysis; 3 trials on cerebellar
stimulation (n = 22; 39 treatment periods); 3 trials on
hippocampal DBS (n = 15; 21 treatment periods); 1 trial on
nucleus accumbens DBS (n = 4; 8 treatment periods); and 1
trial on responsive ictal onset zone stimulation (n = 191; 191
treatment periods). In addition, 1 small RCT (n = 6) compared
6 months of hippocampal DBS versus sham stimulation.
Evidence of selective reporting was present in 4 trials and the
possibility of a carry-over effect complicating interpretation of
the results could not be excluded in 5 cross-over trials without
any or a sufficient wash-out period. Moderate-quality evidence
could not demonstrate statistically or clinically significant
changes in the proportion of patients who were seizure-free or
experienced a 50 % or greater reduction in seizure frequency
(primary outcome measures) after 1 to 3 months of anterior
thalamic DBS in (multi)focal epilepsy, responsive ictal onset
zone stimulation in (multi)focal epilepsy patients and
hippocampal DBS in (medial) temporal lobe epilepsy.
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 40 of 67
However, a statistically significant reduction in seizure
frequency was found for anterior thalamic DBS (mean
difference (MD), -17.4 % compared to sham stimulation; 95 %
CI: -31.2 to -1.0; high-quality evidence), responsive ictal onset
zone stimulation (MD -24.9 %; 95 % CI: -40.1 to -6.0; high-
quality evidence) and hippocampal DBS (MD -28.1 %; 95 %
CI: -34.1 to -22.2; moderate-quality evidence). Both anterior
thalamic DBS and responsive ictal onset zone stimulation did
not have a clinically meaningful impact on QOL after 3 months
of stimulation (high-quality evidence). Electrode implantation
resulted in post-operative asymptomatic intra-cranial
hemorrhage in 1.6 % to 3.7 % of the patients included in the 2
largest trials and 2.0 % to 4.5 % had post-operative soft tissue
infections (9.4 % to 12.7 % after 5 years); no patient reported
permanent symptomatic sequelae. Anterior thalamic DBS was
associated with fewer epilepsy-associated injuries (7.4 versus
25.5 %; p = 0.01) but higher rates of self-reported depression
(14.8 versus 1.8 %; p = 0.02) and subjective memory
impairment (13.8 versus 1.8 %; p = 0.03); there were no
significant differences in formal neuropsychological testing
results between the groups. Responsive ictal-onset zone
stimulation appeared t o be well-tolerated with few side effects.
The limited number of patients precluded firm statements on
safety and tolerability of hippocampal DBS. With regards to
centromedian thalamic DBS, nucleus accumbens DBS and
cerebellar stimulation, no statistically significant effects could
be demonstrated but evidence is of only low to very low
quality. The authors concluded that except for 1very small
RCT, only short-term RCTs on intra-cranial neurostimulation
for epilepsy are available. Compared to sham stimulation, 1 to
3 months of anterior thalamic DBS ((multi)focal epilepsy),
responsive ictal onset zone stimulation ( (multi)focal epilepsy)
and hippocampal DBS (temporal lobe epi lepsy) moderately
reduced seizure frequency in refractory epilepsy patients.
Anterior thalamic DBS was associated with higher rates of
self-reported depression and subjective m emory impairment.
Thee investigators stated that there is insufficient evidence t o
make firm conclusive statements on the safety and efficacy of
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 41 of 67
hippocampal DBS, centromedian thalamic DBS, nucleus
accumbens DBS and cerebellar stimulation. They stated that
there is a need for more, large and well-designed RCTs to
validate and optimize the safety and efficacy of invasive intra-
cranial neurostimulation treatments.
High-Frequency Oscillations in Epilepsy Surgery Planning
Gloss and colleagues (2017) noted that epilepsy is a serious
brain disorder characterized by recurrent unprovoked s eizures.
Approximately 2/3 of seizures can be controlled with anti-
epileptic medications. For some of the others, surgery can
completely eliminate or significantly reduce the occurrence of
disabling seizures. Localization of epileptogenic areas for
resective surgery is far from perfect, and new tools are being
examined to more accurately localize the epileptogenic zone
and improve the likelihood of freedom from post-surgical
seizures. Recordings of pathological high-frequency
oscillations (HFOs) may be one such tool. In a Cochrane
review, these researchers evaluated the ability of HFOs to
improve the outcomes of epilepsy surgery by helping to
identify more accurately the epileptogenic areas of the brain.
For the latest update, these investigators searched the
Cochrane Epilepsy Group Specialized Register (July 25,
2016), the Cochrane Central Register of Controlled Trials
(CENTRAL) via the Cochrane Register of Studies Online
(CRSO, July 25, 2016), Medline (Ovid, 1946 to July 25, 2016),
CINAHL Plus (EBSCOhost, July 25, 2016), Web of Science
(Thomson Reuters, July 25, 2016), ClinicalTrials.gov (July 25,
2016), and the WHO International Clinical Trials Registry
Platform ICTRP (July 25, 2016). They included studies that
provided information on the outcomes of epilepsy surgery for
at least 6 months and which used HFOs in making decisions
regarding epilepsy surgery. The primary outcome of the
review was the Engel Class Outcome System (class I = no
disabling seizures, II = rare disabling seizures, III = worthwhile
improvement, IV = no worthwhile improvement). Secondary
outcomes were responder rate, ILAE epilepsy surgery
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 42 of 67
outcome, frequency of AEs from any source and QOL
outcomes. These researchers intended to analyze outcomes
via an aggregated data fixed-effect model meta-analysis. A
total of 2 studies representing 11 participants met the inclusion
criteria. Both studies were small non-randomized trials, with
no control group and no blinding. The quality of evidence for
all outcomes was very low. The combination of these 2
studies resulted in 11 participants who prospectively used ictal
HFOs for epilepsy surgery decision-making. Results of the post-
surgical seizure freedom Engel class I to IV outcome were
determined over a period of 12 to 38 months (average of
23.4 months) and indicated that 6 participants had an Engel
class I outcome (seizure freedom), 2 had class II (rare
disabling seizures), 3 had class III (worthwhile improvement);
no AEs were reported. Neither study compared surgical
results guided by HFOs versus surgical results guided without
HFOs. The authors concluded that no reliable conclusions
can be drawn regarding the efficacy of using HFOs in epilepsy
surgery decision-making at present.
Feyissa and associates (2018) examined the relationship
between HFOs and the presence of pre-operative seizures,
WHO tumor grade, and isocitrate dehydrogenase 1 (IDH1)
mutational status in gliomas. These investigators
retrospectively studied intra-operative E CoG recorded in 16
patients with brain tumor (12 presenting with seizures) who
underwent awake craniotomy and surgical resection bet ween
September 2016 and June 2017. The number and distribution
of HFOs were determined and quantified visually and with an
automated HFO detector. A total of 5 patients had low-grade
(1 with grade I and 4 with grade II) and 11 had high-grade (6
with grade III and 5 with grade IV) brain tumors. An IDH1
mutation was found in 6 patients. Patients with a history of pre
operative seizures were more likely to have HFOs than those
without pre-operative seizures (9 of 12 versus 0 of 4, p = 0.02).
The rate of HFOs was higher in patients with IDH1 mutant
(mean of 7.2 per minute) than IDH wild-type (mean of
2.3 per minute) genotype (p = 0.03). The authors concluded
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 43 of 67
that HFOs were common in brain tumor-related epilepsy, and
HFO rate may be a useful measure of epileptogenicity in
gliomas.
The authors stated that the retrospective, single-center design
of this study had inherent limitations. The small sample size (n
= 16) limited definitive conclusions to be drawn regarding the
association between HFOs and seizures in brain tumor-related
epilepsy (BTRE). In this cohort, HFOs were not detected
independently of spikes or sharp waves, although in 1 patient
these researchers observed periodic sharp wave discharges
without accompanying HFOs. This raised the question of
whether HFO analysis added any degree of sensitivity over
standard “Berger band” analysis of ECoG in this population.
These observation should, however, be interpreted cautiously,
particularly given the low sampling rate, which might have
resulted in higher-frequency HFOs (fast ripples) being missed.
Oscillations in the gamma frequency range, as seen in the
majority of this cohort, have been implicated in generating
ictal-like discharges in an in-vitro model of epilepsy. Moreover,
locally generated gamma oscillations preceding inter-ictal
discharges have been found to occur more frequently in the
seizure-onset zone in non-tumoral epilepsies. Conversely,
some studies suggested that fast ripples were more reliable
biomarkers for the epileptogenic zone than slower-frequency
oscillations. Although the distinction between the type of HFO
and epileptogenicity is not absolute, it is of interest to examine
if these observations endure in BTRE. Although these
investigators observed that in their cohort HFO-generating
tissue was completely resected (on the basis of post-operative
MRI findings along with intra-operative photos of grid and/or
strip placement), they did not examine the completeness of
resection of HFO-generating tissue because of the lack of
post-resection ECoG in the majority. However, the favorable
seizure freedom outcome of the cohort (9 of 12 become
seizure-free), albeit with a short follow-up period, could reflect
the extent of surgery, with a majority (9 of 12) undergoing
gross-total resection. Indeed, peri-tumoral tissue could be
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 44 of 67
associated with subtle pathologies such as mild forms of
cortical dysplasia that could be highly epileptogenic and may
result in seizure recurrence if left unresected. The authors
stated that future prospective studies assessing the
completeness of resection of HFO-generating tissue vis-`a-vis
seizure freedom outcome in BTRE are needed. Moreover,
they noted that given the short-term post-operative follow-up,
the seizure freedom outcome of this cohort should be
interpreted cautiously. Taken together, given that HFOs were
seen only in those presenting with seizures, the lack of
surgical tailoring using HFOs as a surrogate, and the non-
controlled surgical outcome data, these findings should be
interpreted cautiously; and prospective studies addressing
these issues are needed to reproduce these findings and to
further highlight the clinical utility of HFOs in BTRE.
Examination of Genetic Variations in Refractory Epilepsy to Guide the Selection of Surgical Candidates
Stevelink and colleagues (2018) stated that in recent years,
many different DNA mutations underlying t he development of
refractory epilepsy have been discovered. However, genetic
diagnostics are still not routinely performed during pre-surgical
evaluation and reports on epilepsy surgery outcome for
patients with genetic refractory epilepsy are limited. These
researchers provided an overview of the literature on seizure
outcome following epilepsy surgery in patients with different
genetic causes of refractory epilepsy. They systematically
searched PubMed and Embase pr ior to January 2017 and
included studies describing treatment outcome following
epilepsy surgery in patients with genetic causes of epilepsy.
They excluded studies in which patients were described with
epilepsy due to tuberous sclerosis complex or Sturge-Weber
syndrome (since this extensive body of research has recently
been described elsewhere) and articles in which surgery was
aimed to be palliative. These researchers identified 24 eligible
articles, comprising a total of 82 patients who had undergone
surgery for (mainly childhood-onset) refractory epilepsy due to
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 45 of 67
15 different underlying genetic causes. The success rate of
surgery varied widely across these different genetic causes.
Surgery was almost never effective in patients with epilepsy
due to mutations in genes involved in channel function and
synaptic transmission, whereas surgery was significantly more
successful regarding seizure control in patients with epilepsy
due to mutations in the mTOR pathway. Patients with a lesion
on MRI tended to have higher seizure freedom rates than
those who were MRI-negative. The authors concluded that
although the evidence is still scarce, the findings of this
systematic review suggested that studying genetic variations in
patients with refractory epilepsy could help guide the selection
of surgical candidates.
Furthermore, an UpToDate review on “Surgical treatment of
epilepsy in adults” (Cascino, 2018) does not mention
examination of genetic variants as part of surgical evaluation.
CPT Codes / HCPCS Codes / ICD-10 Codes
Information in the [brackets] below has been added for clarification purposes. Codes requiring a 7th character are represented by "+":
Code Code Description
CPT codes covered if selection criteria are met:
61534 Craniotomy with elevation of bone flap; for
excision of epileptogenic focus without
electrocorticography during s urgery
61536 for excision of epileptic focus, with
electrocorticography during s urgery
61537 for lobectomy, temporal lobe, without
electrocorticography during s urgery
61538 for lobectomy with electrocorticography
during surgery, temporal lobe
Proprietary
61541 for transection of corpus callosum
61543 for partial or subtotal hemispherectomy
61566 Craniotomy with elevation of bone flap; for
selective amygdalohippocampectomy
61863 -
61864
Twist drill, burr hole, craniotomy, or craniectomy
with stereotactic implantation of neurostimulator
electrode array in subcortical site (e.g.,
thalamus, globus pallidus, subthalamic nucleus,
periventricular, periaqueductal gray), without
use of intraoperative microelectrode recording
61867 -
61868
Twist drill, burr hole, craniotomy, or craniectomy
with stereotactic implantation of neurostimulator
electrode array in subcortical site (e.g.,
thalamus, globus pallidus, subthalamic nucleus,
periventricular, periaqueductal gray), with use
of intraoperative microelectrode recording
61880 Revision or removal of intracranial
neurostimulator electrodes[covered f or
intractable seizures]
61885 -
61886
Insertion or replacement of cranial
neurostimulator pulse generator or receiver,
direct or inductive coupling
95836 Electrocorticogram from an implanted br ain
neurostimulator pulse generator/transmitter,
including recording, with interpretation and
written report, up to 30 days [covered for
intractable seizures]
95958 Wada activation test for hemispheric function,
including electroencephalographic (EEG)
monitoring
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 46 of 67
Code Code Description
Proprietary
95970 -
95971
Electronic analysis of implanted neu rostimulator
pulse generator system (eg, rate, pulse
amplitude, pulse duration, configuration of wave
form, battery status, electrode selectability,
output modulation, cycling, impedance and
patient compliance measurements)
95976 -
95977
Electronic analysis of implanted neurostimulator
pulse generator/transmitter (eg, contact group
[s], interleaving, amplitude, pulse width,
frequency [Hz], on/off cycling, burst, magnet
mode, dose lockout, patient selectable
parameters, responsive neurostimulation,
detection algorithms, closed loop parameters,
and passive parameters) by physician or other
qualified hea lth care professional
95978 Electronic analysis of implanted neu rostimulator
pulse generator system (e.g., rate, pulse
amplitude and dur ation, battery status,
electrode selectability and polarity, impedance
and patient compliance measurements),
complex deep brain neurostimulator pulse
generator/transmitter, with initial or subsequent
programming; first hour [covered for intractable
seizures]
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 47 of 67
Code Code Description
Proprietary
95983 Electronic analysis of implanted neu rostimulator
pulse generator/transmitter (eg, contact group
[s], interleaving, amplitude, pulse width,
frequency [Hz], on/off cycling, burst, magnet
mode, dose lockout, patient selectable
parameters, responsive neurostimulation,
detection algorithms, closed loop parameters,
and passive parameters) by physician or other
qualified hea lth care professional; with brain
neurostimulator pulse generator/ transmitter
programming, first 15 minutes face-hyphento-
hyphen face time with physician or other
qualified hea lth care professional [covered f or
intractable seizures]
95984 Electronic analysis of implanted neu rostimulator
pulse generator/transmitter (eg, contact group
[s], interleaving, amplitude, pulse width,
frequency [Hz], on/off cycling, burst, magnet
mode, dose lockout, patient selectable
parameters, responsive neurostimulation,
detection algorithms, closed loop parameters,
and passive parameters) by physician or other
qualified hea lth care professional; with brain
neurostimulator pulse generator/ transmitter
programming, first 15 minutes face-hyphento-
hyphen face time with physician or other
qualified hea lth care professional [covered f or
intractable seizures]
CPT codes not covered for indications listed in the CPB:
38232 Bone marrow harvesting for transplantation;
autologous
38240 Hematopoietic progenitor cell (HPC); allogeneic
transplantation per donor
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 48 of 67
Code Code Description
Proprietary
38241 autologous transplantation
38242 Allogeneic donor lymphocyte infusions
61567 Craniotomy with elevation of bone flap; for
multiple subpial transections, with
electrocorticography during s urgery [subpial
transection surgery]
61798 Stereotactic radiosurgery (particle beam,
gamma ray or linear accelerator); 1 complex
cranial lesion
+ 61799 each additional cranial lesion, complex (List
separately in addition to code for primary
procedure)
61870 Craniectomy for implantation of neurostimulator
electrodes, cerebellar; cortical
64553 Percutaneous implantation of neurostimulator
electrode array; cranial nerve
77371 Radiation treatment delivery, stereotactic
radiosurgery (SRS), complete course of
treatment of cranial lesion(s) consisting of 1
session; multi-source Cobalt 60 based
77372 linear accelerator based
77432 Stereotactic radiation treatment management of
cranial lesion(s) (complete course of treatment
consisting of 1 session)
O ther CPT codes related to theCPB:
95961 -
95962
Functional cortical and subcortical mapping by
stimulation and/or recording of electrodes on
brain surface, or of depth electrodes, to
provoke seizures or identify vital brain
structures
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 49 of 67
Code Code Description
Proprietary
HCPCS codes not covered for indications listed in the CPB:
G0339 Image guided robotic linear accelerator-based
stereotactic radiosurgery, complete course of
therapy in one session, or first session of
fractionated treatment
G0340 Image guided robotic linear accelerator-based
stereotactic radiosurgery, delivery including
collimator changes and custom plugging,
fractionated treatment, all lesions, per session,
second through fifth sessions, maximum 5
sessions per course of treatment
L 8680 Implantable neurostimulator electrode, each
L 8681 Patient programmer (external) for use with
implantable programmable implantable
neurostimulator pulse generator
L 8682 Implantable neur ostimulator radiofrequency
receiver
L 8683 Radiofrequency transmitter (external) for use
with implantable neurostimulator
radiofrequency receiver
L 8685 Implantable neurostimulator pulse generator,
single array, rechargeable, includes extension
L 8688 Implantable neurostimulator pulse generator,
dual array, non-rechargeable, includes
extension
L 8689 External recharging system for battery (internal)
for use with implantable neurostimulator
L 8695 External recharging system for battery
(external) for use with implantable
neurostimulator
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 50 of 67
Code Code Description
Proprietary
S2142 Cord blood-derived stem cell transplantation,
allogenic
S2150 Bone marrow or blood-derived stem cells
(peripheral or umbilical), allogenic or
autologous, harvesting, transplantation, and
related complications; including; pheresis and
cell preparation/storage; marrow ablative
therapy; drugs, supplies, hospitalization with
outpatient follow-up; medical/surgical,
diagnostic, emergency, and rehabilitative
services; and the number of days of pre- and
post-transplant care in the global definition
ICD-10 codes covered if selection criteria are met:
G40.011 -
G40.019
G40.111 -
G40.119
G40.211 -
G40.219
G40.311 -
G40.319
G40.A11 -
G40.A19
G40.B11 -
G40.B19
G40.411 -
G40.419
G40.811 -
G40.812
G40.911 -
G40.919
Epilepsy, intractable
ICD-10 codes not covered for indications listed in the CPB:
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 51 of 67
Code Code Description
Proprietary
G40.001 -
G40.009
G40.101 -
G40.109
G40.201 -
G40.209
G40.301 -
G40.309
G40.A01 -
G40.A09
G40.B01 -
G40.B09
G40.401 -
G40.409
G40.501 -
G40.509
G40.801 -
G40.804
G40.901 -
G40.909
Epilepsy, not intractable
NeuroPace:
CP T codes covered if criteria are met:
61850 Twist drill or burr hole(s) for implantation of
neurostimulator electrodes, cortical
61860 Craniectomy or craniotomy for implantation of
neurostimulator electrodes, cerebral, cortical
61863 Twist drill, burr hole, craniotomy, or craniectomy
with stereotactic implantation of neurostimulator
electrode array in subcortical site (e.g.,
thalamus, globus pallidus, subthalamic nucleus,
periventricular, periaqueductal gray), without
use of intraoperative microelectrode recording,
first array
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 52 of 67
Code Code Description
Proprietary
61864 each additional array (List separately in
addition to primary procedure)
61880 Revision or removal of intracranial
neurostimulator electrodes
61885 Insertion or replacement of cranial
neurostimulator pulse generator or receiver,
direct or inductive coupling; with connection to
a single electrode array
61886 with connection to 2 or more electrode arrays
61888 Revision or removal of cranial neurostimulator
pulse generator or receiver
95836 Electrocorticogram from an implanted br ain
neurostimulator pulse generator/transmitter,
including recording, with interpretation and
written report, up to 30 days
95970 Electronic analysis of implanted neu rostimulator
pulse generator system (eg, rate, pulse
amplitude, pulse duration, configuration of wave
form, battery status, electrode selectability,
output modulation, cycling, impedance and
patient compliance measurements); simple or
complex brain, spinal cord, or peripheral (ie,
cranial nerve, peripheral nerve, sacral nerve,
neuromuscular) neurostimulator pulse
generator/transmitter, without programming
95971 simple spinal cord, or peripheral (ie,
peripheral nerve, sacral nerve, neuromuscular)
neurostimulator pulse generator/transmitter,
with intraoperative or subsequent programming
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 53 of 67
Code Code Description
Proprietary
95977 Electronic analysis of implanted neu rostimulator
pulse generator/transmitter (eg, contact group
[s], interleaving, amplitude, pulse width,
frequency [Hz], on/off cycling, burst, magnet
mode, dose lockout, patient selectable
parameters, responsive neurostimulation,
detection algorithms, closed loop parameters,
and passive parameters) by physician or other
qualified hea lth care professional; with complex
cranial nerve neurostimulator pulse
generator/transmitter programming by physician
or other qualified heal th care professional
95983 Electronic analysis of implanted neu rostimulator
pulse generator/transmitter (eg, contact group
[s], interleaving, amplitude, pulse width,
frequency [Hz], on/off cycling, burst, magnet
mode, dose lockout, patient selectable
parameters, responsive neurostimulation,
detection algorithms, closed loop parameters,
and passive parameters) by physician or other
qualified hea lth care professional; with brain
neurostimulator pulse generator/ transmitter
programming, first 15 minutes face-to- face time
with physician or other qualified health care
professional
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 54 of 67
Code Code Description
Proprietary
95984 Electronic analysis of implanted neu rostimulator
pulse generator/transmitter (eg, contact group
[s], interleaving, amplitude, pulse width,
frequency [Hz], on/off cycling, burst, magnet
mode, dose lockout, patient selectable
parameters, responsive neurostimulation,
detection algorithms, closed loop parameters,
and passive parameters) by physician or other
qualified hea lth care professional; with brain
neurostimulator pulse generator/ transmitter
programming, each additional 15 minutes face-
to-face time with physician or other qualified
health care professional (List separately in
addition to code for primary procedure)
HCP CS codes covered if criteria are met :
C 1767 Generator, neurostimulator (implantable), non-
rechargeable
L 8687 Implantable neurostimulator pulse generator,
dual array, rechargeable, includes extension
L 8688 Implantable neurostimulator pulse generator,
dual array, non-rechargeable, includes
extension
ICD-10 codes covered if selection criteria are met:
G40.011 -
G40.019
Localization-related (focal) (partial) idiopathic
epilepsy and epileptic syndromes with seizures
of localized onset, intractable
G40.111 -
G40.119
Localization-related (focal) (partial)
symptomatic epilepsy and epileptic syndromes
with simple partial seizures, intractable
G40.211 -
G40.219
Localization-related (focal) (partial)
symptomatic epilepsy and epileptic syndromes
with complex partial seizures, intractable
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 55 of 67
Code Code Description
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 56 of 67
Code Code Description
Magnetic resonance-guided laser interstitial thermal therapy (e.g. the NeuroBlate and the Visualase Thermal Therapy System - no specific code :
The above policy is based on the following references:
1. No authors listed. National Institutes of Health
Consensus Conference. Surgery for epilepsy. JAMA.
1990;264(6):729-733.
2. Silfvenius H, Dahlgren H, Jonsson E, et al. Surgery for
epilepsy [summary]. SBU Report No. 110. Stockholm,
Sweden: Swedish Council on Technology Assessment in
Health Care (SBU); 1991.
3. Wilensky A. History of focal epilepsy and criteria for
medical intractability. Neurosurg Clin N Am. 1993;4
(2):193-198.
4. Scheuer ML, Pedley TA. The evaluation and treatment
of seizures. N Engl J Med. 1990;323(21):1468-1474.
5. Sampietro-Colom L, Granados A. Epilepsy surgery.
Executive Summary. Barcelona, Spain: Catalan Agency
for Health Technology Assessment and Research
(CAHTA); November 1993.
6. Bruni J. Epilepsy in adolescents and adults. In: Conn's
Current Therapy. RE Rakel, ed. Philadelphia, PA: W.B.
Saunders, Co.; 1993: 851-860.
7. Engel J Jr. The epilepsies. In: Cecil Textbook of
Medicine. 19th ed. Vol. 2. JB Wyngaarden, LH Smith, JC
Bennett, eds. Philadelphia, PA: W.B. Saunders Co.;
1992; Ch. 483: 2202-2213.
8. So EL. Update on epilepsy. Med Clin North Am.
1993;77(1):203-214.
9. Elwes RD, Dunn G, Binnie CD, Polkey CE. Outcome
following resective surgery for temporal lobe epilepsy:
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 57 of 67
A prospective follow up study of 102 consecutive
cases. J Neurol Neurosurg Psychiatr. 1991;54(11):949-
952.
10. Fuiks KS, Wyler AR, Hermann BP, Somes G. Seizure
outcome from anterior and complete corpus
callosotomy. J Neurosurg. 1991;74(4):573-578.
11. Tinuper P, Andermann F, Villemure JG, et al. Functional
hemispherectomy for treatment of epilepsy associated
with hemiplegia: Rationale, indications, results, and
comparison with callosotomy. Ann Neurol. 1988;24
(1):27-34.
12. Devinsky O, Pacia S. Epilepsy surgery. Neurol Clin.
1993;11(4):951-971.
13. Smith JR, King DW. Current status of epilepsy surgery. J
Med Assoc Ga. 1993;82(4):177-180.
14. Holmes GL. Surgery for intractable seizures in infancy
and early childhood. Neurology. 1993;43(11 Suppl
5):S28-S37.
15. Roberts DW. The role of callosal section in surgical
treatment of epilepsies. Neurosurg Clin N Am. 1993;4
(2):293-300.
16. Adelson PD, Black PM, Madsen JR, et al. Use of
subdural grids and strip electrodes to identify a
seizure locus in children. Pediatr Neurosurg. 1995;22
(4):174-180.
17. Luders H, Hahn J, Lesser RP, et al. Basal temporal
subdural electrodes in the evaluation with patients
with intractable seizures. Epilepsia. 1989;30(2):131-
142.
18. Devinsky O, Sato S, Kufta CV, et al.
Electroencephalographic studies of simple partial
seizures with subdural electrical recordings.
Neurology. 1989;39(4):527-533.
19. Chung SS, Lee KH, Chang JW, Park YG. Surgical
management of intractable epilepsy. Stereotact Funct
Neurosurg. 1998;70(2-4):81-88.
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 58 of 67
20. Gonzalez-Enriquez J, Garcia-Comas L, Conde-
Olasagasti JL. Surgery for epilepsy [summary]. IPE-
98/14 (Public report). Madrid, Spain: Agencia de
Evaluacion de Tecnologias Sanitarias (AETS); 1998.
21. Chilcott J, Howell S, Kemeny A, et al. The effectiveness
of surgery in the management of epilepsy. Guidance
Notes for Purchasers; 99/06. Sheffield, UK: University
of Sheffield, Trent Institute for Health Services
Research; 1999.
22. Alpherts WC, Vermeulen J, van Veelen CW. The wada
test: Prediction of focus lateralization by asymmetric
and symmetric recall. Epilepsy Res. 2000;39(3):239-
249.
23. Bell BD, Davies KG, Haltiner AM, Walters GL.
Intracarotid amobarbital procedure and prediction of
postoperative memory in patients with left temporal
lobe epilepsy and hippocampal sclerosis. Epilepsia.
2000;41(8):992-997.
24. Fernandes MA, Smith ML. Comparing the fused
dichotic words test and the intracarotid amobarbital
procedure in children with epilepsy.
Neuropsychologia. 2000;38(9):1216-1228.
25. Litt B. Brain stimulation for epilepsy. Epilepsy Behav.
2001;2:S61-S67.
26. Loddenkemper T, Pan A, Neme S, et al. Deep brain
stimulation in epilepsy. J Clin Neurophysiol. 2001;18
(6):514-532.
27. Benabid AL, Koudsie A, Benazzouz A, et al. Deep brain
stimulation of the corpus luysi (subthalamic nucleus)
and other targets in Parkinson's disease. Extension to
new indications such as dystonia and epilepsy. J
Neurol. 2001;248(Suppl 3):III37-III47.
28. Diaz-Arrastia R, Agostini MA, Van Ness PC. Evolving
treatment strategies for epilepsy. JAMA. 2002;287
(22):2917-2920.
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 59 of 67
29. Hodaie M, Wennberg RA, Dostrovsky JO, Lozano AM.
Chronic anterior thalamus stimulation for intractable
epilepsy. Epilepsia. 2002;43(6):603-608.
30. Chabardes S, Kahane P, Minotti L, et al. Deep brain
stimulation in epilepsy with particular reference to the
subthalamic nucleus. Epileptic Disord. 2002;4 Suppl
3:S83-S93.
31. Zimmerman RS, Sirven JI. An overview of surgery for
chronic seizures. Mayo Clin Proc. 2003;78(1):109-117.
32. Engel J Jr, Wiebe S, French J, et al. Practice parameter:
Temporal lobe and localized neocortical resections for
epilepsy: Report of the Quality Standards
Subcommittee of the American Academy of
Neurology, in association with the American Epilepsy
Society and the American Association of Neurological
Surgeons. Neurology. 2003;60(4):538-547.
33. Chapell R, Reston J, Snyder D. Management of
treatment-resistant epilepsy. Evidence
Report/Technology Assessment No. 77. Prepared by
the ECRI Evidence-based Practice Center under
Contract No 290-97-0020. AHRQ Publication No. 03-
0028. Rockville, MD: Agency for Healthcare Research
and Quality (AHRQ); May 2003.
34. Theodore WH, Fisher RS. Brain stimulation for
epilepsy. Lancet Neurol. 2004;3(2):111-118.
35. Kerrigan JF, Litt B, Fisher RS, et al. Electrical stimulation
of the anterior nucleus of the thalamus for the
treatment of intractable epilepsy. Epilepsia. 2004;45
(4):346-354.
36. Goodman JH. Brain stimulation as a therapy for
epilepsy. Adv Exp Med Biol. 2004;548:239-247.
37. Nilsen KE, Cock HR. Focal treatment for refractory
epilepsy: Hope for the future? Brain Res Brain Res Rev.
2004;44(2-3):141-153.
38. Weiner HL, Ferraris N, LaJoie J, et al. Epilepsy surgery
for children with tuberous sclerosis complex. J Child
Neurol. 2004;19(9):687-689.
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 60 of 67
39. Marson A, Ramaratnam S. Epilepsy. In: BMJ Clinical
Evidence. London, UK: BMJ Publishing Group; updated
November 2005.
40. Pichon Riviere A, Augustovski F, Cernadas C, et al.
Epilepsy surgery [summary]. Report IRR No. 18.
Buenos Aires, Argentina: Institute for Clinical
Effectiveness and Health Policy (IECS); December 2003.
41. Kelly K, Theodore WH. Prognosis 30 years after
temporal lobectomy. Neurology. 2005;64(11):1974-
1976.
42. Velasco F, Carrillo-Ruiz JD, Brito F, et al. Double-blind,
randomized controlled pilot study of bilateral
cerebellar stimulation for treatment of intractable
motor seizures. Epilepsia. 2005;46(7):1071-1081.
43. Gallo BV. Epilepsy, surgery, and the elderly. Epilepsy
Res. 2006;68 Suppl 1:S83-S86.
44. Morrell M. Brain stimulation for epilepsy: Can
scheduled or responsive neurostimulation stop
seizures? Curr Opin Neurol. 2006;19(2):164-168.
45. Tellez-Zenteno JF, McLachlan RS, Parrent A, et al.
Hippocampal electrical stimulation in mesial temporal
lobe epilepsy. Neurology. 2006;66(10):1490-1494.
46. Halpern C, Hurtig H, Jaggi J, et al. Deep brain
stimulation in neurologic disorders. Parkinsonism
Relat Disord. 2007;13(1):1-16.
47. Boon P, Vonck K, De Herdt V, et al. Deep brain
stimulation in patients with refractory temporal lobe
epilepsy. Epilepsia. 2007;48(8):1551-1560.
48. Pollo C, Villemure JG. Rationale, mechanisms of
efficacy, anatomical targets and future prospects of
electrical deep brain stimulation for epilepsy. Acta
Neurochir Suppl. 2007;97(Pt 2):311-320.
49. Velasco AL, Velasco F, Velasco M, et al. Electrical
stimulation of the hippocampal epileptic foci for
seizure control: A double-blind, long-term follow-up
study. Epilepsia. 2007;48(10):1895-1903.
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 61 of 67
50. Sun FT, Morrell MJ, Wharen RE Jr. Responsive cortical
stimulation for the treatment of epilepsy.
Neurotherapeutics. 2008;5(1):68-74.
51. Bartolomei F, Hayashi M, Tamura M, et al. Long-term
efficacy of gamma knife radiosurgery in mesial
temporal lobe epilepsy. Neurology. 2008;70(19):1658-
1663.
52. Spencer SS. Gamma knife radiosurgery for refractory
medial temporal lobe epilepsy: Too little, too late?
Neurology. 2008;70(19):1654-1655.
53. Barbaro NM, Quigg M, Broshek DK, et al. A
multicenter, prospective pilot study of gamma knife
radiosurgery for mesial temporal lobe epilepsy:
Seizure response, adverse events, and verbal memory.
Ann Neurol. 2009;65(2):167-175.
54. Troster AI. Neuropsychology of deep brain stimulation
in neurology and psychiatry. Front Biosci.
2009;14:1857-1879.
55. Vojtech Z, Vladyka V, Kalina M, et al. The use of
radiosurgery for the treatment of mesial temporal
lobe epilepsy and long-term results. Epilepsia. 2009;50
(9):2061-2071.
56. Malikova H, Vojtech Z, Liscak R, et al. Stereotactic
radiofrequency amygdalohippocampectomy for the
treatment of mesial temporal lobe epilepsy:
Correlation of MRI with clinical seizure outcome.
Epilepsy Res. 2009;83(2-3):235-242.
57. Jobst B. Brain stimulation for surgical epilepsy.
Epilepsy Res. 2010;89(1):154-161.
58. Fountas KN, Kapsalaki E, Hadjigeorgiou G. Cerebellar
stimulation in the management of medically
intractable epilepsy: A systematic and critical review.
Neurosurg Focus. 2010;29(2):E8.
59. Naegele JR, Maisano X, Yang J, et al. Recent
advancements in stem cell and gene therapies for
neurological disorders and intractable epilepsy.
Neuropharmacology. 2010;58(6):855-864.
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 62 of 67
60. Morrell MJ; RNS System in Epilepsy Study Group.
Responsive cortical stimulation for the treatment of
medically intractable partial epilepsy. Neurology.
2011;77(13):1295-1304.
61. DeGiorgio CM, Shewmon A, Murray D, Whitehurst T.
Pilot study of trigeminal nerve stimulation (TNS) for
epilepsy: A proof-of-concept trial. Epilepsia. 2006;47
(7):1213-1215.
62. Tellez-Zenteno JF, Wiebe S. Hippocampal stimulation in
the treatment of epilepsy. Neurosurg Clin N Am.
2011;22(4):465-475.
63. Health Quality Ontario. Epilepsy surgery: An evidence
summary. Ont Health Technol Assess Ser. 2012;12
(17):1-28.
64. Degiorgio CM, Soss J, Cook IA, et al. Randomized
controlled trial of trigeminal nerve stimulation for
drug-resistant epilepsy. Neurology. 2013;80(9):786-
991.
65. Faught E, Tatum W. Trigeminal stimulation: A
superhighway to the brain? Neurology. 2013;80(9):780-
781.
66. Liu C, Wen XW, Ge Y, et al. Responsive
neurostimulation for the treatment of medically
intractable epilepsy. Brain Res Bull. 2013;97:39-47.
67. Ge Y, Hu W, Liu C, et al. Brain stimulation for treatment
of refractory epilepsy. Chin Med J (Engl). 2013;126
(17):3364-3370.
68. Krishnaiah B, Ramaratnam S, Ranganathan LN. Subpial
transection surgery for epilepsy. Cochrane Database
Syst Rev. 2013;8:CD008153.
69. Gloss D, Nolan SJ, Staba R. The role of high-frequency
oscillations in epilepsy surgery planning. Cochrane
Database Syst Rev. 2014;1:CD010235.
70. Heck CN, King-Stephens D, Massey AD, et al. Two-year
seizure reduction in adults with medically intractable
partial onset epilepsy treated with responsive
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 63 of 67
neurostimulation: Final results of the RNS System
Pivotal trial. Epilepsia, **(*):1–10, 2014.
71. Bergey GK, Morrell MJ, Mizrahi EM, et al. Long-term
treatment with responsive brain stimulation in adults
with medically intractable partial onset seizures.
Neurology (submitted), 2014.
72. U.S. Food and Drug Administration (FDA). FDA
approved medical device to treat epilepsy. FDA News
Release. Silver Spring, MD: FDA; November 14, 2013.
73. NeuroPace, Inc. RNS System User Manual. DN1011977
Rev 7. Mountain View, CA: NeuroPace; revised January
2013.
74. NeuroPace, Inc. NeuroPace RNS System Patient
Manual. DN1014634 Rev 3. Mountain View, CA:
NeuroPace; revised November 2013.
75. Engel J Jr, Wiebe S, French J, et al. Practice parameter:
Temporal lobe and localized neocortical resections for
epilepsy. Epilepsia. 2003;44(6):741-751.
76. Maguire M, Marson AG, Ramaratnam S. Epilepsy
(partial). BMJ Clin Evid. 2011;2011. pii: 1214.
77. Kuang Y, Yang T, Gu J, et al. Comparison of therapeutic
effects between selective amygdalohippocampectomy
and anterior temporal lobectomy for the treatment of
temporal lobe epilepsy: A meta-analysis. Br J
Neurosurg. 2014;28(3):374-377.
78. Kovanda TJ, Tubbs RS, Cohen-Gadol AA. Transsylvian
selective amygdalohippocampectomy for treatment of
medial temporal lobe epilepsy: Surgical technique and
operative nuances to avoid complications. Surg Neurol
Int. 2014;5:133.
79. Malikova H, Kramska L, Vojtech Z, et al. Different
surgical approaches for mesial temporal epilepsy:
Resection extent, seizure, and neuropsychological
outcomes. Stereotact Funct Neurosurg. 2014;92
(6):372-380.
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 64 of 67
80. Jobst BC, Cascino GD. Resective epilepsy surgery for
drug-resistant focal epilepsy: A review. JAMA. 2015;313
(3):285-293.
81. Willie JT, Laxpati NG, Drane DL, et al. Real-time
magnetic resonance-guided stereotactic laser
amygdalohippocampotomy for mesial temporal lobe
epilepsy. Neurosurgery. 2014;74(6):569-584;
discussion 584-585.
82. Mathon B, Bedos Ulvin L, Adam C, et al. Surgical
treatment for mesial temporal lobe epilepsy
associated with hippocampal sclerosis. Rev Neurol
(Paris). 2015;171(3):315-325.
83. Chang EF, Englot DJ, Vadera S. Minimally invasive
surgical approaches for temporal lobe epilepsy.
Epilepsy Behav. 2015;47:24-33.
84. Kang JY, Wu C, Tracy J, et al. Laser interstitial thermal
therapy for medically intractable mesial temporal lobe
epilepsy. Epilepsia. 2016;57(2):325-334.
85. Lewis EC, Weil AG, Duchowny M, et al. MR-guided laser
interstitial thermal therapy for pediatric drug-resistant
lesional epilepsy. Epilepsia. 2015;56(10):1590-1598.
86. Tibussek D, Klepper J, Korinthenberg R, et al.
Treatment of infantile spasms: Report of the
Interdisciplinary Guideline Committee Coordinated by
the German-Speaking Society for neuropediatrics.
Neuropediatrics. 2016;47(3):139-150.
87. McCracken DJ, Willie JT, Fernald B, et al. Magnetic
resonance thermometry-guided stereotactic laser
ablation of cavernous malformations in drug-resistant
epilepsy: Imaging and clinical results. Oper Neurosurg
(Hagerstown). 2016;12(1):39-48.
88. LaRiviere MJ, Gross RE. Stereotactic laser ablation for
medically intractable epilepsy: The next generation of
minimally invasive epilepsy surgery. Front Surg.
2016;3:64.
89. Waseem H, Vivas AC, Vale FL. MRI-guided laser
interstitial thermal therapy for treatment of medically
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 65 of 67
refractory non-lesional mesial temporal lobe epilepsy:
Outcomes, complications, and current limitations: A
review. J Clin Neurosci. 2017;38:1-7.
90. van Offen M, van Rijen PC, Leijten FS. Central lobe
epilepsy surgery - (functional) results and how to
evaluate them. Epilepsy Res. 2017;130:37-46.
91. Lagman C, Chung LK, Pelargos PE, et al. Laser
neurosurgery: A systematic analysis of magnetic
resonance-guided laser interstitial thermal therapies. J
Clin Neurosci. 2017;36:20-26.
92. Hoppe C, Witt JA, Helmstaedter C, et al. Stereotactic
laser thermocoagulation in epilepsy surgery.
Nervenarzt. 2017;88(4):397-407.
93. Shukla ND, Ho AL, Pendharkar AV, et al. Laser
interstitial thermal therapy for the treatment of
epilepsy: Evidence to date. Neuropsychiatr Dis Treat.
2017;13:2469-2475.
94. Sprengers M, Vonck K, Carrette E, et al. Deep brain and
cortical stimulation for epilepsy. Cochrane Database
Syst Rev. 2017;7:CD008497.
95. Gloss D, Nevitt SJ, Staba R. The role of high-frequency
oscillations in epilepsy surgery planning. Cochrane
Database Syst Rev. 2017;10:CD010235.
96. Kang JY, Sperling MR. Epileptologist's view: Laser
interstitial thermal ablation for treatment of temporal
lobe epilepsy. Epilepsy Res. 2018;142:149-152.
97. Harward SC, Chen WC, Rolston JD, et al. Seizure
outcomes in occipital lobe and posterior quadrant
epilepsy surgery: A systematic review and meta-
analysis. Neurosurgery. 2018;82(3):350-358.
98. Feyissa AM, Worrell GA, Tatum WO, et al. High-
frequency oscillations in awake patients undergoing b
rain tumor-related epilepsy surgery. Neurology.
2018;90(13):e1119-e1125.
99. Stevelink R, Sanders MW, Tuinman MP, et al. Epilepsy
surgery for patients with genetic refractory epilepsy: A
systematic review. Epileptic Disord. 2018;20(2):99-115.
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 66 of 67
100. Cascino GD. Surgical treatment of epilepsy in adults.
UpToDate Inc., Waltham, MA. Last reviewed December
2018.
Proprietary
Epilepsy Surgery - Medical Clinical Policy Bulletins | Aetna Page 67 of 67
Copyright Aetna Inc. All rights reserved. Clinical Policy Bulletins are developed by Aetna to assist in administering plan
benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial,
general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care
services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors
in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely
responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is
subject to change.
Copyright © 2001-2020 Aetna Inc.
Proprietary
AETNA BETTER HEALTH® OF PENNSYLVANIA
Amendment to Aetna Clinical Policy Bulletin Number: 0394 Epilepsy
Surgery
There are no amendments for Medicaid.
www.aetnabetterhealth.com/pennsylvania annual 06/01/2020
Proprietary